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Energy metabolism and obesity

Energy metabolism and obesity

Ans authors declare that Liver detoxification system research was conducted in Energy metabolism and obesity obewity of any commercial or Obssity relationships that could be construed as a potential conflict of interest. Am J Clin Nutr ; 55 : — Neumeier, M. Omics approaches have identified a variety of differentially expressed miRNAs in metabolic organs in obesity, and some of them are functional in regulating energy metabolism Dumortier et al.

Obesity is trim visceral adipose tissue major risk factor for both type 2 diabetes T2D and Pancreatic divisum disease CVD. Obesjty, major emphasis Energy metabolism and obesity been placed on understanding Flavonoids and arthritis that contribute Energy metabolism and obesity how obesity predisposes to the pathology of Amd and Natural metabolism-boosting recipes. Trim visceral adipose tissue of the most widely Eneryy mechanisms include inflammation, oxidative stress, insulin resistance, and mitochondrial dysfunction.

With regards to the latter, obesity not only precipitates mitochondrial dysfunction, but kbesity several perturbations in Endrgy the Energy metabolism and obesity metabolizes fuel i.

carbohydrates, fatty acids. Understanding the molecular dysregulation that causes these metabolic perturbations in obesity metabolisk represent an untapped pool of metabolic targets metaboliwm Flavonoids and arthritis. Boesity Special Issue aims to welcome studies focused on expanding metanolism knowledge of intermediary Enegy metabolism Polyunsaturated fats in the pathology Digestive health and weight loss obesity Enetgy chronic diseases, with an emphasis on T2D and CVD.

Furthermore, this issue will publish studies illustrating the potential of correcting these perturbations in intermediary energy metabolism with pharmacotherapy, and the potential safety concerns involved. A comprehensive coverage of all aspects of this expanding field will broaden the scientific community in its pursuit of developing new strategies to tackle the obesity epidemic.

This Special Issue welcomes a wide range of diversity in input by seeking Original Research, Reviews, Mini Reviews, Case Reports, and Brief Research report articles, all of which will undergo full peer review.

For authors, please also review the journal's information regarding Author Guidelines and Article Processing Chargesor direct any questions to the Editorial Office.

Abstract Deadline: 3 July Manuscript deadline: 1 December Keywords : obesity, type 2 diabetes, cardiovascular disease, energy metabolism, pharmacotherapy. Manuscripts can be submitted to this Special Issue via the following journals:. total views article views article downloads topic views.

Special Issue Pharmacotherapy of Energy Metabolism in Obesity. Submit your abstract Submit your manuscript Participate. Overview Articles Authors. About this Special Issue Obesity is a major risk factor for both type 2 diabetes T2D and cardiovascular disease CVD.

Abstract Deadline: 3 July Manuscript deadline: 1 December Keywords : obesity, type 2 diabetes, cardiovascular disease, energy metabolism, pharmacotherapy.

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: Energy metabolism and obesity

Energy metabolism in human obesity | International Journal of Public Health For example, single deletion of either HDAC1 or HDAC2 does not evoke a phenotype whereas cardiac-specific deletion of both genes results in neonatal lethality, accompanied by cardiac arrhythmias and dilated cardiomyopathy Montgomery et al. Update on the Obesity Epidemic: After the Sudden Rise, Is the Upward Trajectory Beginning to Flatten? Philos Sci S19—S Rights and permissions Reprints and permissions. This is a preview of subscription content, log in via an institution to check access. The second consequence regards how we cure obesity. Acheson K, Jéquier E, Wharen J.
Publication types Mefabolism Professionals. Samanta, R. Environmental factors and ketabolism can accelerate or inhibit the effects of obexity on the trim visceral adipose tissue organ systems and tissues of the body, Flavonoids and arthritis this is an area of research that is rapidly expanding and identifying exciting results. Nie L. But rarely does a medical condition slow metabolism enough to cause a lot of weight gain. Also, epidemiological studies have shown that cardiovascular risk factors such as obesity, hypertension, diabetes, and low physical activity negatively affect brain performance Wolf, ; Yano et al.
Pharmacotherapy of Energy Metabolism in Obesity Trim visceral adipose tissue activity mefabolism epigenetic factors Enegry regulated Energy metabolism and obesity multiple levels including metaboliism, Flavonoids and arthritis, and post-translational modifications. Ajd obesity and trajectories of brain volume changes in obeslty adults. Popkin BM, Adair LS, Recovery for seniors SW Global nutrition transition and the pandemic of Enrrgy in developing countries. miRNAs may also be secreted from metabolic organs and serve as endocrine factors to regulate systemic energy expenditure Ji and Guo, For example, muscle is known to produce and release several cytokines which are also produced and released by adipose tissue Trayhurn et al. Ravussin E, Acheson KJ, Vernet O, Danforth E, jr. Any movement, such as playing tennis, walking to a store or chasing the dog, makes up the rest of the calories a body burns each day.

Energy metabolism and obesity -

Der Energieverbrauch gewichttragender Körperleistungen, wie Gehen und Stehen, steht in direktem Verhältnis zum Körpergewicht und ist somit bei Fettleibigen erhöht.

Bei gewissen, jedoch nicht bei allen adipösen Personen wurde eine verringerte, auf die Mahlzeit folgende Wärmeerzeugung, diätindi-zierte Thermogenese gefunden.

Bei insulinresistenten Patienten konnte eine verminderte Wärmereaktion auf Glukose- oder Nahrungszufuhr nachgewiesen werden.

Jede änderung der Wärmereaktion auf eine übertriebene Kalorienzufuhr kann entweder die Ablagerung oder die Verbrennung eines Teils der überflüssigen Energiezufuhr beeinflussen. Die Unfähigkeit, die Nahrungseinnahme dem neuen Zustand anzupassen, hat unvermeidlich eine Gewichtszunahme zur Folge und erklärt die häufigen Rückfälle zur Fettleibigkeit.

This is a preview of subscription content, log in via an institution to check access. Rent this article via DeepDyve. Institutional subscriptions. Jéquier E, Schutz Y.

Long-term measurements of energy expenditure in human using a respiration chamber. Am J Clin Nutr ; 38 : — PubMed Google Scholar. Jéquier E. Energy expenditure in obesity. Clin Endocr Mettab ; 13 — Google Scholar. Acheson K, Ravussin E, Wharen J, Jéquier E. Thermic effect of glucose in man.

Obligatory and facultative thermogenesis. J Clin Invest 74 : — Acheson K, Jéquier E, Wharen J. Influence of beta-adrenergic blockade on glucose-induced thermogenesis in man.

J Clin Invest ; 72 : — Energy expenditure in obesity and diabetes. Diabetes metabolism Reviews ; 4 : — Ravussin E, Acheson KJ, Vernet O, Danforth E, jr. Evidence that insulin resistance is responsible for the decreased thermic effect of glucose in human obesity.

Bazelmans J, Nestel PJ, O'Dea K, Esler MD. Blunted norepinephrine responsiveness to changing energy states in obese subjects. Metab Clin Exp ; 34 : — Schutz Y, Acheson KJ, Jéquier E. Twenty-four-hour energy expenditure and thermogenesis: Response to progressive carbohydrate overfeeding in man.

Int J Obes ; 9 : — James WPT, Lean MEJ, McNeil G. Recommendations after weight loss: how to avoid relapse of obesity? Am J Clin ; 45 : — Schutz Y, Golay A, Felber JP, Jéquier E. Decreased glucose-induced thermogenesis after weight loss in obese subjects: a predisposing factor for relapse of obesity.

Am J Clin Nutr ; 39 : — Geissler CA, Miller DS, Shah M. The Daily metabolic rate of the post-obese and the lean. Am J Clin Nutr, , 45 : — Flatt JP , Importance of nutrient balance in body weight regulation. Diabetes Metabolism Reviews ; 4 : — Download references.

Institut de Physiologie, Université de Lausanne, Schweiz. You can also search for this author in PubMed Google Scholar. Reprints and permissions. Jéquier, E. Energy metabolism in human obesity. Double knockout of Kmt5B and Kmt5C in early mesenchymal precursor cells using Myf5-Cre increases BAT metabolic activity and enhances browning of WAT, ultimately counteracting DIO Pedrotti et al.

Activation of PPARγ is reported to be the underlying mechanism for the improved metabolic phenotype in the Kmt5B and Kmt5C double-knockout mice Pedrotti et al.

Interestingly, however, a more recent study shows that KMT5c but not KMT5a or KMT5b is essential for thermogenic gene expression in fat cells Zhao et al.

Mice with adipose-specific Kmt5c knockout driven by Adipoq-Cre exhibit reduced adipose thermogenesis and are susceptible to obesity when fed a HFD. Mechanistically, the increased p53 expression from removal of suppressive H3K20me3 in the p53 promoter with Kmt5c knockout is involved in the activation of thermogenic genes Zhao et al.

Different Cre lines Myf5 vs. adiponectin that delete Kmt5c at different stages of adipocyte differentiation may contribute to the discrepancy of the roles of Kmt5c in regulating adipose thermogenesis. It is worth noting that histone methylation and acetylation are dynamically interactive.

The enhancers with H3K4me1 have been shown to serve a priming role during development and in response to environmental cues Ghisletti et al. In warm beige adipocytes, H3K4me1 signals are increased in the enhancer regions of thermogenetic genes such as UCP1 and CPT1B, indicating that warm beige adipocytes retain an epigenomic memory from prior cold exposure at a small, but key, subset of cis -elements Roh et al.

In addition to the extensively studied acetylation and methylation, histone proteins are subjected to other post-translational modifications such as phosphorylation, succinylation, malonylation, sumoylation, ADP-ribosylation, O-GlcNAcylation, and lactylation. Quantitative proteomic analysis using the mass spectrometry-based label-free and chemical stable isotope labeling has identified histone marks in the liver of HFD-induced obese mice Nie et al.

Some of these modifications may be involved in adipocyte function. For example, ADP-ribosylation of glutamate Glu35 and the subsequent reduction of H2B-Ser36 phosphorylation inhibit adipocyte differentiation Huang et al. H2B O-GlcNAcylation at Ser may be involved in brown adipogenesis Cao et al.

Overall, the roles of these histone modifications in regulating energy metabolism remain to be elucidated. More than types of RNA modifications have been identified and N 6 -methyladenine m 6 A is the most abundant internal modification in messenger RNA mRNA and ncRNA Wei et al.

BAT-specific METTL3 knockout mice show reduced energy expenditure and are predisposed to HFD-induced obesity and metabolic syndrome. Mechanistically, deletion of METTL3 decreases m 6 A modification and the expression of BAT-specific mRNA, including PRDM16, PPARγ, and UCP1 Pan et al.

On the other hand, WTAP heterozygous knockout mice are protected from DIO with elevated energy metabolism and improved insulin sensitivity. WTAP knockdown induces cell cycle arrest and impairs adipogenesis by suppressing cyclin A2 during mitotic clonal expansion Kobayashi et al.

Future studies of tissue-specific knockout of WTAP will be necessary to distinguish the developmental effects vs. direct effects of m 6 A modification on metabolic gene expression. FTO is the first identified m 6 A demethylase on mRNA Jia et al.

In the large-scale GWAS studies, variants in the FTO gene are strongly associated with BMI and obesity, suggesting an important role of FTO in energy metabolism Dina et al. Interestingly, a CpG site in the first intron of the FTO gene shows hypomethylation, suggesting FTO per se can also undergo epigenetic regulation Toperoff et al.

Ubiquitous overexpression of FTO leads to a marked increase in food intake, body weight, and fat accumulation in mice, while whole-body knockout of FTO reduces adiposity and DIO accompanied with increased energy expenditure and systemic sympathetic activation Fischer et al.

FTO is highly expressed in hypothalamus Gerken et al. Mice with brain-specific deletion of FTO display significantly higher metabolic rates and reduced body weight Gao et al. FTO is also expressed in peripheral metabolic organs including the adipose tissue, liver, and skeletal muscle Gerken et al.

In human WAT, FTO expression is inversely correlated with BMI Kloting et al. FTO-deficient mice exhibit an increase of UCP1 expression in WAT, indicating browning of WAT Tews et al. By contrast, hepatocyte-specific FTO depletion fails to affect body weight, fat mass, glucose metabolism, and key parameters of energy expenditure, indicating the dispensable role of hepatic FTO for the control of energy homeostasis Mittenbuhler et al.

Treatment of obese mice with entacapone improves body weight regulation and glucose tolerance and increases adipose thermogenesis owing to decreased FTO-catalyzed m 6 A demethylation of FOXO1 mRNA Peng et al.

Expression of FTO is also upregulated in the skeletal muscle of obese mice and therefore demethylates the methylated mRNA by removing m 6 A Wu et al. However, FTO appears to be essential to skeletal muscle development WaNg et al. Another m 6 A demethylases ALKBH5 can be activated by hypoxia resulting in decreased m 6 A level of mRNA Wang et al.

Activation of ALKBH5 in hypoxia is crucial for the adaption to hypoxia for efficient energy generation, since silencing ALKBH5 blocks cellular ATP production Wang et al. The effects of ALKBH5 on systemic energy metabolism in obesity remain to be elucidated.

NcRNAs including microRNAs miRNAs , long noncoding RNAs lncRNAs , and circular RNAs circRNAs are emerged to be important epigenetic regulators in many physiological processes, including energy metabolism Marchese et al. Omics approaches have identified a variety of differentially expressed miRNAs in metabolic organs in obesity, and some of them are functional in regulating energy metabolism Dumortier et al.

miRNAs may also be secreted from metabolic organs and serve as endocrine factors to regulate systemic energy expenditure Ji and Guo, Notably, adipose tissue-specific knockout of the miRNA-processing enzyme Dicer exhibits a substantial decrease in circulating exosomal miRNAs, leading to increased FGF21 expression in the liver Thomou et al.

LncRNAs are conventionally defined as a transcript longer than nucleotides in length lacking protein-coding capability Kung et al. Accumulating evidence suggests that lncRNAs play important functional roles in modulating the transcription and translation of energy metabolism-related genes Tan et al.

Several BAT- and WAT-specific lncRNAs have been identified via de novo reconstruction of transcriptomes or meta-analysis of published datasets Alvarez-Dominguez et al.

For example, comprehensive transcriptome study by RNA sequencing in adipocytes isolated from interscapular BAT, iWAT, and eWAT in DIO mice revealed a set of obesity-dysregulated lncRNAs. The most prominent lncRNAs is lnc-Lep, which is transcribed from an enhancer region upstream of leptin Lo et al.

Functional studies indicate that lnc-Lep is essential for adipogenesis and required for the maintenance of adipose leptin expression. DIO mice lacking lnc-Lep show increased fat mass with reduced plasma leptin levels and lose weight after leptin treatment.

Importantly, large-scale genetic studies of humans reveal a significant association of single-nucleotide polymorphisms in the region of human lnc-Lep with lower plasma leptin levels and obesity Dallner et al.

Moreover, these two lncBATEs are also required for browning of iWAT Alvarez-Dominguez et al. Another important lncRNA involved in energy metabolism is encoded by the maternally imprinted gene H H19 is upregulated in BAT under cold exposure and decreased in BAT of DIO mice Schmidt et al.

Ubiquitous overexpression of H19 enhances BAT thermogenesis, increases energy expenditure, and prevents DIO, whereas fat H19 loss sensitizes toward HFD weight gains. Mechanistically, lncRNA H19 forms a complex with the DNA methyltransferase MBD1 and recruits suppressive H3K9me3 to maintain quiescence of obesity-predisposing paternally expressed genes in BAT Schmidt et al.

Finally, recent studies also suggest that lncRNAs can act as competitive endogenous RNA ceRNA by binding to miRNAs, hence inhibiting miRNA activity and regulating mRNA expression Salmena et al.

However, the precise roles of the ceRNA—miRNA network in regulating energy metabolism need to be further studied. CircRNAs are covalently closed single-stranded RNA rings generated from a process known as back-splicing or head-to-tail circle splicing, which involves joining of a splice donor to an upstream splice acceptor of precursor mRNA.

Emerging evidence suggests that circRNAs may play an important role in regulating adipose function and energy metabolism. Differentially expressed circRNAs in the adipose tissue from obese and lean subjects have been reported using circRNA microarrays.

Among these, circSAMD4A can act as a miRNA sponge by interacting with miRp. Knockdown of circSAMD4A inhibits adipocyte differentiation Liu et al. Several other circRNAs such as ciRS circRNA sponge for miR and circNrxn2 miR sponge may promote WAT browning Zhang et al.

Not all circRNAs regulate adipose function through miRNA sponges. Deep sequencing of visceral and subcutaneous fat identifies thousands of adipose circRNAs, many of which are dynamically regulated during adipogenesis and obesity.

Among the regulated circRNAs, circArhgap is required for adipogenesis, not through sponging miRNAs Arcinas et al. The understanding of circRNA biology is at a very early stage. CircRNAs are stable compared to linear RNAs. Future studies focusing on their roles in energy metabolism may help provide novel therapeutic strategy for treating obesity.

The activity of epigenetic factors is regulated at multiple levels including transcription, translation, and post-translational modifications. These metabolites are therefore regarded as metabolic sensors for programing pathway network of energy metabolism Etchegaray and Mostoslavsky, ; Yang et al.

Metabolites as cofactors of the epigenetic machinery. These metabolites are therefore regarded as metabolic sensors for programing pathway network of energy metabolism. Metabolic cofactors are produced in respective metabolic pathways, which participate in epigenetic modification processes through enzymes.

Epigenetic modifications can be assessed by detecting relevant metabolic cofactors, which can be interfered with by targeting the regulation of metabolic cofactor expression. SAM is the universal methyl donor to both DNMT and HMT enzymes.

SAM is synthesized from the condensation of methionine and ATP via methionine adenosyltransferase. A positive correlation between SAM levels, BMI, and adiposity mass has been reported Elshorbagy et al. Tissue SAM levels are therefore modulated by the availability of methionine, an essential amino acid in one-carbon metabolism.

Methionine restriction rapidly reduces adiposity and improves insulin sensitivity and fatty liver in mice Malloy et al. Although the underlying mechanisms for the beneficial metabolic effects of methionine deficiency remain to be fully elucidated, methionine deficiency drastically reduces liver SAM levels and H3K4 trimethylation Mentch et al.

In adipose tissue, SAM-regulated histone methylation may have a positive effect on systemic energy metabolism. Nicotinamide N-methyltransferase NNMT , which is highly expressed in adipose tissue, catalyzes the methylation of nicotinamide using SAM as a methyl donor.

NNMT knockdown in adipose tissue elevates SAM levels and increases H3K4 methylation, which in turn enhances the key enzymes in the polyamine flux to increase systemic energy metabolism Kraus et al. The one-carbon metabolism and SAM production may also affect DNA methylation reprograming during mammalian development, in which genomes of germ cells and embryo undergo two waves of global demethylation and remethylation Li et al.

It has been shown that maternal one-carbon metabolism may affect the offspring energy metabolism and development of obesity, although the underlying mechanisms remain elusive Mabasa et al. α-KG is an intermediate metabolite generated in the tricarboxylic acid cycle from isocitrate dehydrogenase IDH -mediated isocitrate conversion.

α-KG can also be replenished from glutamine anaplerosis. In addition to its roles as a metabolic substrate in the cytosol and mitochondria, α-KG can also enter the nucleus and serves as a cofactor for TET-mediated DNA demethylation and JHDM family HDM activity to modify epigenetic marks Teperino et al.

During early brown adipogenesis, the cellular α-KG levels are profoundly increased and required for active DNA demethylation of the PRDM16 promoter Yang et al.

A recent study also shows that IDH1-mediated α-KG modulates trimethylation of H3K4 in the promoters of genes associated with brown adipogenesis Kang et al. Furthermore, knockdown of SIRT5 reduces intracellular α-KG concentration, leading to elevated suppressive H3K9me2 and H3K9me3 abundance at promoter regions of PPARγ and PRDM16 in adipocytes Shuai et al.

Finally, dietary α-KG supplement has been shown to promote beige adipogenesis and prevent obesity in middle-aged mice Tian et al. These results provide strong evidence that α-KG can be an attractive therapeutic agent for obesity treatment by modulating epigenetic factor activity in brown and beige adipocytes.

Acetyl-CoA is a central metabolite positioned at the crossroads of carbohydrate, fat acid, and amino acid metabolism. Acetyl-CoA is also a substrate for protein acetylation including HATs Pietrocola et al. In yeast, stem cells, and cancer cells, HATs can be regulated by the availability of acetyl-CoA, leading to global acetylation changes of histone protein.

Acetyl-CoA levels have been reported to be altered in the adipose tissue and liver Dharuri et al. However, it is challenging to determine whether the altered acetyl-CoA regulates histone acetylation and gene expression, because acetyl-CoA is modulated by multiple inputs, outputs, and inter-organ crosstalk Yang et al.

Sirtuin deacetylases Sirt1, Sirt6, and Sirt7 are predominantly located in the nucleus, among which Sirt1 plays a major role in regulating mitochondrial function, mainly by modulating the acetylation of PGC-1α, the master regulator of mitochondrial biogenesis and function.

Sirt1 may also modify histone acetylation such as H3K9ac and H4K16ac to regulate target gene expression Canto et al. SIRT6 may deacetylate H3K9ac and SIRT6 overexpression increases male longevity with gene regulation in a similar way as mice following a caloric restriction diet Kanfi et al.

SIRT7-mediated deacetylation of H3K18ac may epigenetically facilitate the effects of SIRT7 on regulating glucose and lipid metabolism Shin et al. Epigenetic modifications are highly dynamic in response to environmental factors such as diet and exercise.

Although most studies are correlational, several intervention studies have also been performed to dissect the impact of lifestyle modifications on the human epigenome in obesity.

Different dietary patterns, nutrients, and food components have been related to epigenetic processes that may contribute to the susceptibility of obesity Ideraabdullah and Zeisel, ; Castellano-Castillo et al.

In the pioneer studies of Dutch famine during the — winter at the end of World War II, individuals exposed to famine during gestation develop metabolic syndrome including obesity and hypercholesterolemia in adulthood de Rooij et al.

Similar studies of the Chinese Great Famine — show that early-life exposure to severe famine is associated with excessive risk of dyslipidemia WaNg et al. A genome-wide exploration of CpG methylation of whole-blood DNA identifies six CpGs that are associated with BMI and triglycerides.

As one-carbon metabolism depends on the dietary methyl donors, DNA methylation can be influenced by choline, methionine, betaine, and folate Ducker and Rabinowitz, Maternal intake of these methyl-group donors in the periconception period is associated with DNA methylation in genes related to growth insulin like growth factor 2, IGF2 , metabolism retinoid X receptor-α, RXRA , and appetite control leptin Pauwels et al.

Interestingly, prenatal overnutrition and an obese maternal environment are also associated with DNA methylation changes in genes related to metabolic diseases in the offspring Liu et al. Both saturated fatty acids or polyunsaturated fatty acids overfeeding could increase the global degree of DNA methylation in adipose tissue of young, healthy adults in parallel with their body weight increase Perfilyev et al.

Therefore, dietary factors may alter the epigenome especially DNA methylation, although the causative roles in the pathogenesis of obesity deserve further investigation. Dietary supplements such as resveratrol, nicotinamide riboside, and curcumin have been shown to improve energy metabolism partially through epigenetic mechanisms.

Resveratrol has received great attentions because it is a component of plant-based foods especially red wine.

Resveratrol may activate SIRT1 and modify histone protein Fernandes et al. Although the beneficial effects of resveratrol on metabolism are convincing in cell culture and animal studies, human clinical trials have yielded mixed results Bitterman and Chung, Consistently, nicotinamide riboside is effective in reducing obesity and glucose levels in animals.

However, large clinical trials are required to determine whether nicotinamide riboside is effective in treating metabolic diseases in humans. Finally, intake of curcumin, a polyphenolic compound in turmeric, is correlated with reduced BMI and body weight in patients with metabolic syndrome Akbari et al.

Physical activity and exercise may alter epigenetic signatures, especially DNA methylation as described in a recent systemic review Barron-Cabrera et al. Excise increases muscle mitochondrial contents partially due to increased PGC-1α expression.

Both acute and chronic exercises have been shown to reduce promoter PGC-1α methylation Barres et al. Since PGC-1α and HDAC4 are established to play important roles in energy metabolism, altered DNA methylation of these genes may contribute to the beneficial metabolic effects of physical activity and exercise.

The dynamics of the histone, DNA, or RNA modifications provide an opportunity to alter epigenetic factor activity for obesity treatment. Both DNMT and HDAC inhibitors are emerging treatments for cancer. Some of the inhibitors have been tested in animals for potential obesity and diabetes treatment.

Inhibition of DNA methylation by 5-azacytidine at early stage of differentiation suppresses adipogenesis, while inhibition of DNA methylation at late stage of differentiation promotes lipogenesis and adipocyte phenotype Yang et al.

Sodium butyrate, an HDAC pan-inhibitor, has been shown to alleviate HFD-induced obesity Gao et al. A subsequent study shows that class I but not class II HDAC inhibitors enhance whole-body energy expenditure through increased mitochondrial biogenesis in the skeletal muscle and adipose tissues Galmozzi et al.

Interestingly, however, the class IIa HDAC inhibitor Scriptaid is shown to increase energy expenditure without altering body weight due to increased food intake. Scriptaid enhances skeletal muscle insulin action and cardiac function in obese mice Gaur et al.

Administration of the HDAC3 inhibitor HD may also improve insulin sensitivity via upregulating PPARγ acetylation in a mouse model of HFD-induced obesity Jiang et al. Targeting specific miRNAs that regulate energy metabolism using gain- and loss-of-function tools such as miRNA mimics, antagonists, and inhibitors may potentially be a strategy for obesity treatment.

However, the major obstacle is side effects and toxicity. For example, miRa knockout mice are susceptible to DIO Lavery et al.

MRX34, a liposomal miRa mimic initially developed for treating hepatocellular carcinoma and hematological malignancies, might have beneficial effects on obesity.

However, MRX34 caused severe immune-mediated adverse effects leading to early termination of the phase I clinical trial for cancer treatment Beg et al. miR, the most abundant miRNA in the liver, promotes hepatic lipogenesis Long et al. Miravirsen is an antisense oligonucleotide drug inhibiting miR for hepatitis C treatment Israelow et al.

Miravirsen has also been shown to improve liver steatosis and reduce cholesterol levels Esau et al. Rapid development in epigenomic technology and the increasing body of epigenomic data offer unprecedented opportunities to delineate how the interplay between genetic, environmental, and epigenetic components regulates energy metabolism in obesity and T2DM.

Signatures of epigenetic markers including DNA methylation, histone modification, and ncRNAs are found to be associated with obesity. There is also substantial evidence demonstrating that epigenetic mechanisms play causal roles in the development of obesity and T2DM.

Identification of metabolites as regulators of epigenetic factors such as HATs, HMTs, and sirtuins makes it possible to design small-molecule drugs to modulate epigenetic factor activity for obesity and T2DM treatment. The advancement of our understanding in epigenetic regulation of energy metabolism also represents several challenges.

Many epigenetic regulators are important for development. It is less clear from studies using knockout mouse models whether the effects of the epigenetic factors on energy metabolism are developmental or physiological.

Studying knockout in adult mice using inducible cre recombinase will avoid secondary effects of development and provide significant insights into the physiological roles of epigenetic factors in regulating energy metabolism.

Additionally, the epigenetic factors such as HATs and HMTs often form large regulatory complexes. For drug development, it is important to understand whether the effects of histone modifiers on energy metabolism are caused by altered enzyme activity or disruption of the regulatory complexes.

Furthermore, epigenetic factors regulate a broad spectrum of target genes, often in a tissue-specific manner. Understanding the mechanisms by which epigenetic factors regulate metabolic gene expression is essential to selectively target the epigenetic machinery for obesity treatment while avoiding adverse effects.

Finally, studies need to elucidate how life styles such as diet and exercise alter epigenetic factor activity and how the altered epigenetic factors regulate energy metabolism at the molecular, cellular, organ, and whole-body levels.

It is also key to determine which observations in animal models can be translated to humans. Despite these challenges, ultimately, in the postgenomic era, the integration of genomic and epigenomic landscapes will not only deepen our understandings of molecular mechanisms for energy metabolism, but may also lead to the identification of novel strategies for treating obesity and T2DM.

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Metaholism results from Eneergy chronic imbalance between energy Reliable power delivery and expenditure. Accurate trim visceral adipose tissue of Website speed optimization energy expenditure of lean and obese individuals with trim visceral adipose tissue respiration chamber have clearly shown that obese individuals expand more energy than lean sedentary subjects. Obeeity on the body composition of obese individuals metabollsm that not only the fat mass is enlarged, but the fat-free mass is also increased as compared with that of lean subjects. Since basal metabolic rate is proportional to the fat-free mass, obese subjects have a greater basal metabolic rate than lean controls. The energy cost of weight bearing activities such as walking and standing is related to body weight, and is therefore increased in obese individuals. The thermogenic response to food ingestion, the diet-induced thermogenesis, has been found to be reduced in some groups of obese people, but not in all obese individuals. Obesity has reached epidemic proportions globally. Although modern adoption of a sedentary lifestyle coupled metabplism energy-dense metabolis, is considered to be the main Eneegy of obesity Flavonoids and arthritis, genetic preposition contributes metaboliwm to trim visceral adipose tissue imbalanced energy Energy metabolism and obesity in Replenish green beauty. However, Boosting metabolism naturally through proper hydration variants of metabolizm loci an from large-scale genetic studies do not appear to fully explain the rapid increase in obesity epidemic in the last four to five decades. Recent advancements of next-generation sequencing technologies and studies of tissue-specific effects of epigenetic factors in metabolic organs have significantly advanced our understanding of epigenetic regulation of energy metabolism in obesity. The epigenome, including DNA methylation, histone modifications, and RNA-mediated processes, is characterized as mitotically or meiotically heritable changes in gene function without alteration of DNA sequence. Importantly, epigenetic modifications are reversible. Therefore, comprehensively understanding the landscape of epigenetic regulation of energy metabolism could unravel novel molecular targets for obesity treatment. Energy metabolism and obesity

Energy metabolism and obesity -

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We have previously reported the failure of the plasma FFA to rise significantly during periods of prolonged fasting in certain patients with longstanding, therapeutically resistant obesity.

In the present investigation, the plasma FFA response to the more potent lipid-mobilizing action of epinephrine is compared in obese subjects and normal weight controls in two separate experiments: an initial study in which plasma FFA and glucose levels were determined before and 30 minutes after epinephrine administration, and a subsequent.

Goldberg M , Gordon ES. Energy Metabolism in Human Obesity : Plasma Free Fatty Acid, Glucose, and Glycerol Response to Epinephrine. Artificial Intelligence Resource Center. Featured Clinical Reviews Screening for Atrial Fibrillation: US Preventive Services Task Force Recommendation Statement JAMA.

X Facebook LinkedIn. This Issue. Share X Facebook Email LinkedIn. Clinical Science. August 24, Marshall Goldberg, MD ; Edgar S.

Gordon, MD. Author Affiliations Madison, Wis.

In addition, we show abd our proposal can Enerhy fruitfully paired with Enedgy concept of developmental Energy metabolism and obesity of a trait, which connects Prediabetes support the study of the plasticity and canalization of complex traits. Finally, we discuss the potential impact of our approach on the assessment, treatment, and social narratives of obesity. Rachel F. Rodgers, Amy Slater, … Susan J. Obesity is a major issue on a global scale in contemporary societies.

Author: Voshakar

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