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Caloric restriction and fat metabolism

caloric restriction and fat metabolism

JS, Inflammation and exercise, NNX, caloric restriction and fat metabolism PLW restrictjon equally to metablism caloric restriction and fat metabolism. Lee SK Sex as caloric restriction and fat metabolism important biological variable in biomedical Lycopene and skin rejuvenation BMB Reports 51 — Article PubMed PubMed Central Google Mettabolism Gong Q, Zhang P, Wang J, Ma J, An Y, Chen Y, et al. Obesity: global epidemiology and pathogenesis. Among others, target genes are i the adenosine triphosphate-binding cassette transporter ABCA1 member 1 of human transporter subfamily ABCAwhich mediates the efflux of cholesterol, ii the fatty acid synthase FASwhich catalyzes the synthesis of fatty acids from acetyl-CoA and malonyl-CoA, and the iii sterol regulatory element—binding protein-1c SREBP-1cwhich regulates genes of the cholesterol metabolism 14—

Caloric restriction and fat metabolism -

This can lead to anemia and extreme fatigue 16 , 17 , In addition, the number of carbs you eat may play a role in fatigue.

Some studies suggest that calorie-restricted diets with low amounts of carbs may cause feelings of fatigue in some individuals 19 , 20 , 21 , However, other studies find that low-carb diets reduce fatigue.

Therefore, this effect may depend on the individual 23 , To prevent fatigue and nutrient deficiencies, avoid overly restricting your calories and ensure you eat a variety of whole, minimally processed foods.

Restricting calories too severely can lead to fatigue. Maintaining this calorie restriction for too long can also lead to nutrient deficiencies.

Restricting calories too dramatically can negatively affect fertility. This is especially true for women, as the ability to ovulate depends on hormone levels. More specifically, an increase in estrogen and luteinizing hormone LH levels is needed in order for ovulation to occur 31 , An insufficient calorie intake may also reduce estrogen levels, which is thought to have lasting negative effects on bone and heart health 34 , 35 , Signs of reduced fertility may include irregular menstrual cycles or a lack of them.

However, subtle menstrual disturbances may not have any symptoms, so they may require a more thorough medical examination to be diagnosed 37 , Overly restricting calories may potentially reduce fertility, especially in women.

More studies are needed to determine the effects of calorie restriction in men. Consuming too few calories can weaken your bones. Low levels of these two reproductive hormones are thought to reduce bone formation and increase bone breakdown, resulting in weaker bones 40 , 41 , 42 , In addition, calorie restriction — especially when combined with physical exercise — can increase stress hormone levels.

This may also lead to bone loss Bone loss is especially troublesome because it is often irreversible and increases the risk of fractures 45 , Restricting calories may disturb hormone levels, which may result in weaker bones and an increased risk of fractures.

For instance, one study compared athletes in disciplines that put a strong emphasis on body leanness, such as boxing, gymnastics or diving, to those in disciplines less focused on body weight. The researchers reported that athletes in disciplines that required leanness made more frequent attempts to lose weight and were almost twice as likely to have been sick in the previous three months In another study, taekwondo athletes who were dieting to reduce their body weight in the week before a competition experienced reduced immunity and an increased risk of infection The effects of calorie restriction in non-exercising individuals are less clear, and more research is needed before strong conclusions can be made Calorie restriction, especially when combined with strenuous physical activity, may lower your immune defenses.

Calorie needs vary from person to person because they depend on factors such as age, sex, height, current weight and physical activity level. There are various ways to estimate your own calorie needs. The easiest method consists of three simple steps:. In addition, make sure you record what you eat in an online food journal like Cronometer , at least in the beginning of your weight loss process.

Tracking your diet will help you ensure that you continue to reach your daily recommended nutrient intakes. When it comes to long-term weight loss, patience is key. Instead, opt for diets that are focused on diet quality and encourage you to make sustainable lifestyle changes.

In order to lose weight, you need to eat fewer calories than you burn. Here are 35 simple but highly effective ways to cut lots of calories. Calories matter, but counting them is not at all necessary to lose weight.

Samples were boiled for 5 min, cooled on ice for 1 min, vortexed, and equal amounts of protein 13 µg per lane separated on gradient polyacrylamide gels Bio-Rad, Hercules, CA, USA. Samples were then transferred to Immobilon-FL transfer membrane Millipore, Billerica, MA, USA. Fluorescent color was detected with Odyssey CLx Imager LI-COR, Lincoln, NE, USA.

Band signal was quantified using Image Studio v5. Quantified data obtained from two different membranes were combined by using the strength of the signal of the ladder bands as a control for intensity differences between the two membranes. Liver ceramide and dihydroceramide content was determined using LC-MS Lipidomics Core Facility; University of the Highlands and the Islands, Inverness, UK.

As per Folch et al. Fifty microlitres of each sample was combined with μL ceramide 1 μM in MeOH and 25 μL dihydroceramide 2 μM in MeOH; Avanti Polar Lipids, Alabaster, AL, USA as internal standards. MeOH 1. Samples were then stored on ice for 1 hr with intermittent vortex mixing, centrifuged at rpm for 5 min at 4 °C and the supernatant was collected.

KCl 0. The lower phase was collected and evaporated under nitrogen and reconstituted in 1 mL CHCl 3. The column was conditioned twice with 3 mL CHCl 3 and then loaded with 1 mL of the sample. The collected eluate was evaporated and dried under vacuum and reconstituted in μL MeOH.

The ceramides and dihydroceramides were separated on a Kinetex C8 HPLC column 1. Mobile phase B was The flow rate used was μL per min at 40 °C. Total ceramide and dihydroceramide concentrations were calculated from the summed concentrations of all the monitored molecular species.

All values were normalised to wet weight of liver. RNA was isolated from tissues using Ribozol solution cat. RNA quantity and quality were quantified using a NanoDrop spectrophotometer Thermo Fisher Scientific,USA and RNA Integrity Number RIN was assessed using Agilent RNA Pico Kit and an Agilent bioanalyzer Agilent, USA.

Library preparation and sequencing was performed by BGI Shenzhen, Guangdong, China ; bp pair-end sequencing was done using a DNBseq-G MGI Tech.

edu using STAR v2. Mapped reads were counted using featureCounts in Subread package v1. Count data were normalised and analysed using DESeq2 v1.

Principal component analysis was performed using the prcomp function for genes with the highest variation among samples after transforming the raw count data using the vst function from the DESeq2 package.

For GSEA, a gene set collection including eight gene sets was used for Figure 7C ; further details are in Table 3.

Heatmaps were drawn with Morpheus. Data were analysed for normal distribution using the Shapiro-Wilk normality test. Normally distributed data were analysed by ANOVA, mixed models or t-tests, as appropriate; mixed models were used for repeated-measures analyses in which some data points were missing or had to be excluded for some mice.

Where data were not normally distributed, non-parametric tests were used. When appropriate, p values were adjusted for multiple comparisons. Data are presented as mean ± SEM or as Violin plots, as indicated in the figure legends. All statistical analyses were performed using Prism software GraphPad, USA.

Raw data from RNA sequencing have been depositied at NCBI's GEO repository with accession number GSE In the interests of transparency, eLife publishes the most substantive revision requests and the accompanying author responses.

In this study we reveal that, in both mice and humans, the metabolic benefits of caloric restriction CR are sex- and age-dependent. Our results have critical implications for understanding the fundamental biology linking diet and health outcomes, as well as translational strategies to leverage the therapeutic benefits of CR in humans.

We hope the Editorial Board will agree on the value and importance of our study, which we have further improved through the revisions described below. In addition, we have conducted extensive new calorimetry studies using the Promethion CORE system, which is the highest-resolution system available for indirect calorimetry.

These new data, along with our lipolysis analyses, explain why females resist weight loss and fat loss during caloric restriction. Description of the revisions that have already been incorporated in the transferred manuscript.

A The clinical part is definitely the weak spot in the study. I don't think that the data should be omitted, but the authors should be very careful in interpreting the data. Obvious limitations apply to this part, which need to be more directly addressed in the abstract and discussion.

It feels like the data from the small-scale clinical trial is exaggerated. Her group are experts in the study of dietary interventions for weight loss.

The study was conducted to a high standard and therefore we have the utmost confidence in the conclusions drawn from our analysis of this data. This explains some of the limitations that the reviewer mentions, e.

the relatively low numbers of younger males, and the focus on overweight and obese subjects. As requested, we have now addressed these limitations as follows:.

Updated the abstract to clarify that the data are from overweight and obese subjects. Updated the results to emphasise that we did a retrospective analysis of CR in overweight and obese subjects lines Performed an additional ANCOVA analysis to test if baseline adiposity or BMI contribute to the sex differences in body mass, fat mass or fat-free mass new Figure 10—figure supplement 1 ; see Reviewer 1 Major Point D below.

Updated the Methods to again clarify the retrospective nature of the analysis lines B It is important to mention in the abstract and the discussion that the human data came from obese participants.

This might well influence the findings from human data. The human subjects were overweight or obese; this was previously stated in the methods section line and in the discussion lines To further clarify this, we now also mention it in the Abstract line 62 and have reiterated it in the Discussion line Importantly, the fact that humans still show age-dependent sex differences in fat loss, even when overweight and obese, supports our conclusion that this age effect in mice is not simply a consequence of aged mice being fatter than younger mice.

In response to point D below, we have also analysed if the loss of fat mass or fat-free mass is influenced by adiposity or BMI at baseline pre-CR. Our analyses show that neither of these parameters explain the sex differences in loss of fat mass or fat-free mass see new Figure 10—figure supplement 1.

This is crucial information to compare it to other studies. D Since there is quite a wide range in the BMIs of the participants, can the authors also stratify against BMI?

We now present this data in Figure 10—figure supplement 1. We find that, in males but not in females, baseline BMI or fat mass are significantly associated with the changes in fat mass or fat-free mass: surprisingly, individuals with higher baseline fat mass or BMI show less fat loss and a greater loss of fat-free mass during CR.

Importantly, males and females do not significantly differ in the relationships between baseline fat mass or BMI and loss of fat mass or fat-free mass. This further supports our conclusion that the sex differences in fat loss are unrelated to differences in baseline adiposity.

We report this in lines of the Results and lines of the Discussion. E There is no mention of any pre-study registration online of the clinical part e. Was this done? In the updated manuscript we now state this on lines of the Methods, as well as in the Results line and Discussion lines F In the methods section the authors write "Participants were informed that the study was funded by an external commercial sponsor…".

This is important information, and this is not mentioned anywhere else in the paper. Can the authors clarify this point? A commercial sponsor would, in my view, qualify for a conflict of interest that needs to be mentioned.

G How did the authors determine the group sizes for the clinical part? I have some doubts about the sub-group sizes. It would be valuable information if the authors had a statistical analysis plan prior conducting the study.

It appears a bit, like the sub-groups were chosen at random, to match findings of the mouse data. Otherwise, there should have been a better allocation within the sub-groups especially age. We agree that larger group sizes would have been preferable. This limitation reflects that the study was not originally designed to test age and sex effects on CR outcomes, but instead was analysed retrospectively to investigate the impact of these variables.

As mentioned above, we have updated the text of the manuscript to highlight the retrospective nature of the analyses. H There's a big problem with the age stratification of the male participants in the clinical data. Although this looks intriguing, this can easily be a sampling problem.

We used 45 years as the cut-off point because this is the age when, in women, oestrogen levels begin to decline as was stated in lines of the Discussion, and now reiterated in lines of the Results. I The applied protocol for CR in mice is known to provoke long fasting phases and probably elicits some effects through fasting alone, rather than the caloric deficit.

There are some papers out addressing this e. by deCabo, Lamming. The authors should not dismiss this fact and at least address it in their discussion. Also, given this fact, it would be thoughtful to include a database-search — not only regarding CR — but also regarding various types of intermittent fasting protocols in humans and animal studies similar to what the authors did in the supplemental figure.

We have added a new paragraph to the Discussion to address this Lines Regarding the second point, we feel that including a new literature search that addresses not only CR, but also intermittent fasting, is beyond the scope of the current manuscript. However, this is a very good idea and would be worth addressing in a future standalone review article.

We have also updated our source data to include all data from our literature reviews, to help if other researchers wish to analyse according to fasting duration or other variables. We have since done this in new cohorts of mice fed using the same CR protocol. We find that the mice consume their food within hours, consistent with other CR studies.

We have now mentioned this in the Methods section lines K While CR certainly has a lot of health benefits in rodents and humans, it should be advised to raise the cautious note that it may not be beneficial for everyone in the general population.

For some groups of people and in some cases e. This should be mentioned clearly, as the topic gets more and more "hyped" in public media and online.

We now highlight this important point in the opening paragraph of the introduction lines L There is no indication of how the authors dealt with missing data. Statistically this can be very important, especially in cases with a low number of data points.

For analyses involving paired or repeated-measures data e. time courses of body mass or blood glucose , if data points were missing or had to be excluded for some mice then we used mixed models for the statistical analysis.

Because of the large numbers of mice used in our studies, analyses remain sufficiently well powered even if some data points were missing or had to be excluded. M Key data from qPCR should be followed up by western blots or other means.

If this was done and there was no effect, the authors should report this. Also, is there any evidence or the possibility to support these findings regarding pck1 and ppara in human samples? We have now used RNA sequencing to comprehensively determine how CR and sex influence the hepatic transcriptome.

These data are reported in new Figures 7 and Figure 7—figure supplement 1 of the revised manuscript. The data identify extensive sex differences in how CR alters hepatic function. Gene set enrichment analysis shows that CR stimulates oxidative phosphorylation and the TCA cycle in males but not in females, even though, in both sexes, there is increased fatty acid oxidation.

Moreover, we find that plasma ketone concentrations, a marker of hepatic acetyl-CoA levels, are increased in females compared to males.

Thus, our data suggest that CR males use hepatic acetyl-CoA to support the TCA cycle, whereas, in females, acetyl-CoA accumulates, thereby activating pyruvate carboxylase and stimulating gluconeogenesis.

These new data substantially improve our manuscript and highlight unexpected sex differences that may underpin the metabolic and health benefits of CR. Regarding effects of CR on PCK1 and PPARA expression in human liver samples, no human CR studies have taken liver biopsies for downstream molecular analysis.

Recent studies of the GTEx database confirm that hepatic gene expression in humans is highly sexually dimorphic Oliva et al. The effect of CR on their hepatic expression, and whether this differs between males and females, remains to be addressed.

N : I think it would be very valuable to analyse the sex-differences in lipolysis directly in fat tissues. The authors concentrated on differences in hepatic mRNA profiles, but there's an obvious possibility and gap in their story.

We agree and have now analysed lipolysis in two ways: firstly, by measuring plasma non-esterified fatty acids NEFA , and secondly by measuring phosphorylation of hormone-sensitive lipase HSL in adipose tissue.

In the Discussion we cite previous research identifying sex differences in adipose lipolysis and lipogenesis and explain how this data fits with our findings lines O Given the relatively low n and sometimes small effect sizes I fear that some of their findings won't be reproduced by other labs.

The mouse data were pooled from across multiple cohorts, with ANOVA confirming that the same sex-dependent CR effects were observed within each cohort.

This reproducibility across multiple cohorts is a clear strength of our study because it demonstrates the robustness of our findings. a The discussion is very extensive, and I suggest compressing the information presented there to make it more easily readable.

We have removed some text that was more speculative, such as the paragraph discussing a possible role for ERalpha. We have also revised wording elsewhere to state things more succinctly. However, given the scope of our study we feel we cannot substantially cut down the Discussion without compromising the interpretation of our findings.

Recently some reviews have summarized the different forms e. Longo Nature Aging, Hofer Embo Mol Med, … and the authors should address this briefly. Especially the applied CR intervention in mice overlaps with intermittent fasting. We have updated the Discussion lines to explain how our single-ration CR protocol also incurs a prolonged intermittent fast, and how this fast per se may contribute to metabolic effects.

We used 45 years as the cut-off point because this is the age when, in women, oestrogen levels begin to decline this point was stated in lines of the Discussion, and we now reiterate it in lines of the Results.

f The part on aging starting in Figure 7 comes quite surprising and it is not clearly linked to the data before. We have added a sentence to smooth the transition to these studies lines , linking the rationale to findings from the RNAseq data that is shown in the previous section.

We had previously done a literature search to identify the age of onset of CR interventions in mice and humans. We summarise the findings of this search in lines and of the Discussion.

We have also updated the source data so that it includes our review of the CR literature, allowing other researchers to interrogate this data. g At the first mention of HOMA and Matsuda indices, the effect direction should be put into physiological context.

We have updated the Methods to explain that the PCA analyses were done using R. We have updated the source data to include the outputs from these analyses, as well as the underlying code. i Were the mice aged in-house in the authors' facility or bought pre-aged from a vendor?

Is it known how they were raised? If bought pre-aged, were female and male animals comparable? We bred and aged all mice in house. Males and females were littermates from across several cohorts.

Therefore, there are no concerns about lack of comparability resulting from environmental differences. j Very minor note: I think that "focussed" has become very rarely used, even in British English. I don't know about the journal's language standards, but I would switch to the much more common "focused".

We have also updated the figure legends to specify this. l Limitations section: Maybe tone down on "world-leading mass spec facility". This sounds like an excuse and this statement is unsupported and doesn't add anything valuable to the section. Other limitations would include the low n, as mentioned above and the mono-centric fashion of the mouse and human experiments.

that includes elements of both CR and intermittent fasting. Point 2: Since the authors fed the animals in the morning, this is likely the reason for energy expenditure to be different in the CR vs ad lib groups. Although the authors do study the effects of night v day feeding and saw no change in the outcomes regarding weight, this fact I think should be mentioned somewhere.

Also, figure 4A is expressed a W while all the other graphs are in kJ. I think it would be nice to see it all consistent. Regarding the first point, we agree that time of feeding can influence when energy expenditure is altered, but most studies show that CR decreases overall energy expenditure regardless of time of feeding.

For example, Dionne et al. studied the effects of CR on energy expenditure, administering the CR diet during the night phase Dionne et al. They found that CR mice have lower energy expenditure in the day but not in the night Figure 3C in their paper , which is the opposite to our findings previous Figure 4C; new figures 3A-B.

However, total energy expenditure in their study remains decreased with CR. We have updated our manuscript Lines to clarify this. The figure legend also reflects this. Point 3: For all the graphs, can you make the CR groups bold and not filled as it is hard to see the lighter colours.

We have updated the graphs so that the CR groups are represented by solid lines, rather than dashed lines. Point 4: I know many investigators use them, but I am not sure how relevant HOMA-IR and the Matsuda index are in mice since they were specifically designed for humans.

Importantly, we are not using the absolute values for HOMA-IR or Matsuda in the same way that they are used in humans; instead, we are comparing the relative values between groups because these are still physiologically meaningful. We discussed this with Dr Sam Virtue, an expert in mouse metabolic phenotyping Virtue and Vidal-Puig, , who agrees on their usefulness in this way.

Point 5: Something also to note is the fact that all the glucose uptake data is under basal conditions. I think that this needs to be discussed and the muscle and fat not completely discounted as a player in the differences seen.

We agree that CR can enhance insulin-stimulated glucose uptake, but our OGTT data suggest that it is effects on fasting glucose, rather than insulin-stimulated glucose uptake, that contribute to the sex differences we observe.

Major point I: … it would be thoughtful to include a database-search — not only regarding CR — but also regarding various types of intermittent fasting protocols in humans and animal studies similar to what the authors did in the supplemental figure.

We feel that including a new literature search that addresses not only CR, but also intermittent fasting, is beyond the scope of the current manuscript. To assist with this, we have updated the source data to include all details of the literature review presented in Figure 1.

The link to the source data is provided in the manuscript. Minor point c: The order of the subpanels in Figure 9 and other figures where B is below A and so on is confusing. Please rearrange or indicate in a visual way which panels belong to each other.

We disagree that the order of subpanels in Figure 9 now Figure 10 is confusing: the panels are clearly labelled, and we find it most logical to have the absolute values shown in the top row panels A, C and E , with the corresponding graphs of fold changes shown beneath each of these panels B, D and F.

This allows the reader to quickly compare the absolute vs fold-change data for each readout. If we had panels A-C on the top row and D-F on the second row, then the connection between graphs 10C and 10D would be less clear and comparable.

Minor point d: Did the authors also measure cardiovascular e. blood pressure parameters? This would be a nice add-on to the rather small clinical data here.

In our human study we measured blood pressure and heart rate before starting CR and at weeks 3 and 4 post-CR. For this response to reviewers we have summarized these human data in Author response image 1. The data show that CR decreases blood pressure and heart rate in males and females Author response image 1A-E.

However, unlike for the effects on fat mass or fat-free mass now shown in Figure 10H-I; previously Figure 9 , across all subjects ANCOVA reveals no age-sex interactions in these cardiovascular effects.

We have decided to not include these data in the current study because we feel it is already extensive and is focused on metabolic outcomes. We instead plan to report the cardiovascular outcomes from both humans and mice in a separate paper. Twenty male and twenty-two female volunteers participated in a weight loss study involving a 4-week dietary intervention, as described for Figure 9.

A-F Systolic blood pressure BP , diastolic BP and heart rate were recorded at weeks 0, 3 and 4. Data are shown as absolute values A,C,E or fold-change relative to baseline B,D,F. G-I Simple linear regression of age vs fold-change week 4 vs week 0 in systolic BP G , diastolic BP H and heart rate I.

In G , similar slopes but different intercepts show that sex significantly influences changes in systolic BP, but the influence of age does not differ between the sexes. In H,I neither slopes nor intercepts differ significantly between males and females, indicating that the age-outcome relationship is similar between the sexes.

Overall P values for each variable, and their interactions, are shown beneath each graph. Dionne, D. Caloric Restriction Paradoxically Increases Adiposity in Mice With Genetically Reduced Insulin.

Endocrinology , Martin, A. Tissue losses and metabolic adaptations both contribute to the reduction in resting metabolic rate following weight loss.

Oliva, M. The impact of sex on gene expression across human tissues. Science , eaba Virtue, S. GTTs and ITTs in mice: simple tests, complex answers. Nat Metab 3 , The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

For the purpose of Open Access, the authors have applied a CC BY public copyright license to any Author Accepted Manuscript version arising from this submission.

CF and AMJ gratefully acknowledge financial support from the Scottish Government as part of the RESAS Strategic Research Programme at the Rowett Institute, University of Aberdeen. Finally, this manuscript was written entirely by the authors and without any use of large language models.

This article is distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use and redistribution provided that the original author and source are credited.

Article citation count generated by polling the highest count across the following sources: Crossref , PubMed Central , Scopus. The cerebellum has been implicated in the regulation of social behavior. Its influence is thought to arise from communication, via the thalamus, to forebrain regions integral in the expression of social interactions, including the anterior cingulate cortex ACC.

However, the signals encoded or the nature of the communication between the cerebellum and these brain regions is poorly understood. Here, we describe an approach that overcomes technical challenges in exploring the coordination of distant brain regions at high temporal and spatial resolution during social behavior.

We developed the E-Scope, an electrophysiology-integrated miniature microscope, to synchronously measure extracellular electrical activity in the cerebellum along with calcium imaging of the ACC.

This single coaxial cable device combined these data streams to provide a powerful tool to monitor the activity of distant brain regions in freely behaving animals. During social behavior, we recorded the spike timing of multiple single units in cerebellar right Crus I RCrus I Purkinje cells PCs or dentate nucleus DN neurons while synchronously imaging calcium transients in contralateral ACC neurons.

We found that during social interactions a significant subpopulation of cerebellar PCs were robustly inhibited, while most modulated neurons in the DN were activated, and their activity was correlated with positively modulated ACC neurons.

These distinctions largely disappeared when only non-social epochs were analyzed suggesting that cerebellar-cortical interactions were behaviorally specific. Our work provides new insights into the complexity of cerebellar activation and co-modulation of the ACC during social behavior and a valuable open-source tool for simultaneous, multimodal recordings in freely behaving mice.

The function of the smooth muscle cells lining the walls of mammalian systemic arteries and arterioles is to regulate the diameter of the vessels to control blood flow and blood pressure.

Although experimental data suggest that K V 1. In female cells, which have larger K V 2. In summary, we present a new model framework to investigate the potential sex-specific impact of antihypertensive drugs.

Spinal muscular atrophy SMA is a neuromuscular disorder characterized by the deficiency of the survival motor neuron SMN protein, which leads to motor neuron dysfunction and muscle atrophy. In addition to the requirement for SMN in motor neurons, recent studies suggest that SMN deficiency in peripheral tissues plays a key role in the pathogenesis of SMA.

Using limb mesenchymal progenitor cell MPC -specific SMN-depleted mouse models, we reveal that SMN reduction in limb MPCs causes defects in the development of bone and neuromuscular junction NMJ.

Specifically, these mice exhibited impaired growth plate homeostasis and reduced insulin-like growth factor IGF signaling from chondrocytes, rather than from the liver. Furthermore, the reduction of SMN in fibro-adipogenic progenitors FAPs resulted in abnormal NMJ maturation, altered release of neurotransmitters, and NMJ morphological defects.

Transplantation of healthy FAPs rescued the morphological deterioration. Our findings highlight the significance of mesenchymal SMN in neuromusculoskeletal pathogenesis of SMA and provide insights into potential therapeutic strategies targeting mesenchymal cells for the treatment of SMA.

Share this article Doi. Cite this article Karla J Suchacki Benjamin J Thomas Yoshiko M Ikushima Kuan-Chan Chen Claire Fyfe Adriana AS Tavares Richard J Sulston Andrea Lovdel Holly J Woodward Xuan Han Domenico Mattiucci Eleanor J Brain Carlos J Alcaide-Corral Hiroshi Kobayashi Gillian A Gray Phillip D Whitfield Roland H Stimson Nicholas M Morton Alexandra M Johnstone William P Cawthorn The effects of caloric restriction on adipose tissue and metabolic health are sex- and age-dependent.

Full text Figures and data Side by side Abstract Editor's evaluation Introduction Results Discussion Materials and methods Data availability References Decision letter Author response Article and author information Metrics.

sa0 Decision letter eLife's review process. Figure 1 with 1 supplement see all. Download asset Open asset. Figure 1—source data 1 Literature search to identify sex differences in mouse and human CR research. Download elifefig1-data1-v2. Figure 2 with 4 supplements see all.

Figure 2—source data 1 Female mice resist weight loss, fat loss, and lipolysis during CR. Download elifefig2-data1-v2. Figure 3 with 2 supplements see all. Figure 3—source data 1 CR decreases energy expenditure and stimulates postprandial lipogenesis more in female than in male mice.

Download elifefig3-data1-v2. Figure 4 with 1 supplement see all. Figure 4—source data 1 The effects of CR on glucose homeostasis differ between young male and female mice.

Download elifefig4-data1-v2. Figure 5 with 1 supplement see all. Beneficial Effects of Time-Restricted Eating on Metabolic Diseases: A Systemic Review and Meta-Analysis. Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al.

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Download references. This research was funded by the Zhejiang Provincial Natural Science Foundation of China under Grant No. LQ23H and LGF21H, and Provincial-Municipal Joint Construction of Key Medical Disciplines In Zhejiang Province ss-xxgbx. Department of Cardiology, The Affiliated Hospital of Jiaxing University, Jiaxing, Zhejiang, , China.

Jiaxing University Master Degree Cultivation Base, Zhejiang Chinese Medical University, Jiaxing, Zhejiang, , China. You can also search for this author in PubMed Google Scholar. J-CS, Z-TT and C-JH contributed to the study design, the data acquisition, analysis, interpretation, the drafting, and revision of the manuscript and agreed to be accountable for all aspects of the work.

C-LZ contributed to the study conceive, the supervision, data interpretation, and performed revision of the manuscript. GQ and H-LH contributed to the study conceive, design, data analysis, interpretation, and revised the manuscript.

All authors read and approved the final manuscript. Correspondence to Gang Qian. Open Access This article is licensed under a Creative Commons Attribution 4. Reprints and permissions. Sun, JC. et al. Time-restricted eating with calorie restriction on weight loss and cardiometabolic risk: a systematic review and meta-analysis.

Eur J Clin Nutr 77 , — Download citation. Received : 24 March Revised : 06 July Accepted : 12 July Published : 24 July Issue Date : November Anyone you share the following link with will be able to read this content:.

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Skip to main content Thank you for visiting nature. nature european journal of clinical nutrition review articles article. Download PDF. Subjects Lifestyle modification Nutrition Obesity Weight management. This article has been updated. Abstract The effect of time-restricted eating TRE has been summarized in previous studies, but its benefits in combination with calorie restriction CR still need to be determined.

Introduction Obesity prevalence has climbed over the past few decades in most nations and has doubled in 73 countries [ 1 ]. Search strategy PubMed, Embase and Cochrane Library were searched from inception to October 18, , for potentially relevant studies without restriction applied to language, publication year, or region using the following search terms: intervention time-restricted eating, feeding, fasting, or diet and outcome blood pressure or diastolic pressure or systolic pressure or diastolic blood pressure or systolic blood pressure or glucose or insulin or homeostatic model assessment for insulin resistance or glucose or insulin or HOMA-IR or HOMA-β or cholesterol or triglyceride or triglycerides or Triacylglycerol or Triacylglycerols or plasma lipid or weight loss or weight losses or weight reduction or weight reductions.

Data extraction Study selection was performed in two phases: an initial title and abstract screening followed by a complete text examination of papers for suitability in this research.

Risk of bias and certainty of evidence assessment Two reviewers JCS and ZTT independently evaluated the risk of bias in selected studies using the revised Cochrane risk of bias tool for randomized trials ROB2 [ 28 ].

Data analysis Stata Statistical Software version Results Search results After removing duplicates, records were retrieved during the initial and updated search. Flow diagram showing search strategy and inclusion and exclusion of studies for meta-analysis. Full size image. Table 1 Characteristics of included studies.

Full size table. A Summary of risk of bias. B Quality assessment percentages in the meta-analysis. A Body weight. B Waist circumference. C Fat mass. A Systolic blood pressure. B Diastolic blood pressure. A Fasting glucose.

B Insulin. C HOMA-IR. D HOMA-β. A Total cholesterol. B Triglyceride. C Low-density lipoprotein. Table 2 Subgroup analysis of weight loss and body composition.

Discussion This systematic review and meta-analysis of 8 trials involving participants revealed that participants who follow a combined TRE and CR regimen efficiently lose body weight and substantially reduce their WC and fat mass.

Conclusion Our systematic review and meta-analysis demonstrated that calorie-intake restriction with time restriction could significantly decrease body weight, fat mass, and WC. Data availability Because this is a meta-analysis, all of the data included in this study can be found in the included references.

References GBD Obesity Collaborators, Afshin A, Forouzanfar MH, Reitsma MB, Sur P, Estep K, et al. Article PubMed PubMed Central Google Scholar Bray GA, Frühbeck G, Ryan DH, Wilding JP. Article PubMed Google Scholar Hoddy KK, Marlatt KL, Çetinkaya H, Ravussin E, et al.

Article Google Scholar Varady KA, Cienfuegos S, Ezpeleta M, Gabel K. Article Google Scholar Schübel R, Nattenmüller J, Sookthai D, Nonnenmacher T, Graf ME, Riedl L, et al. Article PubMed PubMed Central Google Scholar Antoni R, Johnston KL, Steele C, Carter D, Robertson MD, Capehorn MS.

Article CAS Google Scholar Davoodi SH, Ajami M, Ayatollahi SA, Dowlatshahi K, Javedan G, Pazoki-Toroudi HR. Google Scholar Cai H, Qin YL, Shi ZY, Chen JH, Zeng MJ, Zhou W, et al.

Nutrition affects all physiological processes occurring in our body, including eestriction related to the function of the caloric restriction and fat metabolism system; indeed, metabolism has been metabplism associated caloric restriction and fat metabolism the differentiation metabloism activity of reshriction innate and adaptive immune cells. While excessive energy intake Natural liver support adiposity have been caloric restriction and fat metabolism to caloric restriction and fat metabolism rrestriction inflammation, several clinical caloirc experimental Swimming exercises show that calorie restriction Swimming exercisesnot leading to malnutrition, is able caloric restriction and fat metabolism Reserving Berry Flavors aging and exert potent anti-inflammatory effects restricgion different pathological conditions. This review provides an overview of the ability of different CR-related nutritional strategies to control autoimmune, cardiovascular, and infectious diseases, as tested by preclinical studies and human clinical trials, with a specific focus on the immunological aspects of these interventions. In particular, we recapitulate the state of the art on the cellular and molecular mechanisms pertaining to immune cell metabolic rewiring, regulatory T cell expansion, and gut microbiota composition, which possibly underline the beneficial effects of CR. Although studies are still needed to fully evaluate the feasibility and efficacy of the nutritional intervention in clinical practice, the experimental observations discussed here suggest a relevant role of CR in lowering the inflammatory state in a plethora of different pathologies, thus representing a promising therapeutic strategy for the control of human health. This article is part of the Spotlight issue on Obesity, Metabolism, and Diabetes. Over the last few decades, lifestyle in the most industrialized countries has undergone profound changes, in particular in the eating habits.


The ONLY Legit Ways to Lose Fat While Sleeping (the rest is BS) We include products we think are useful for our caloric restriction and fat metabolism. If you buy fatt links on this page, metabolissm may earn a small commission. Caloric restriction and fat metabolism only Anti-inflammatory herbal remedies you Counteract fatigue naturally and products caloruc we stand behind. However, Swimming exercises calories too severely can lead to a variety of health problems, including reduced fertility and weaker bones. A calorie is defined as the amount of heat energy needed to raise the temperature of one gram of water by 1°C 1. Your body requires calories to function and uses them to sustain three main processes 1 :. Generally speaking, eating more calories than your body needs will cause you to gain weightmostly in the form of body fat. caloric restriction and fat metabolism

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