Mechanisms of mitochondrial respiratory adaptation

Nature Reviews Molecular Cell Biology, Journal Year: 2022, Volume and Issue: 23(12), P. 817 - 835

Published: July 8, 2022

Language: Английский

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SIRT1 promotes lipid metabolism and mitochondrial biogenesis in adipocytes and coordinates adipogenesis by targeting key enzymatic pathways

Scientific Reports, Journal Year: 2021, Volume and Issue: 11(1)

Published: April 14, 2021

Abstract The NAD + -dependent deacetylase SIRT1 controls key metabolic functions by deacetylating target proteins and strategies that promote function such as overexpression or boosters alleviate complications. We previously reported SIRT1-depletion in 3T3-L1 preadipocytes led to C-Myc activation, adipocyte hyperplasia, dysregulated metabolism. Here, we characterized SIRT1-depleted adipocytes quantitative mass spectrometry-based proteomics, gene-expression biochemical analyses, mitochondrial studies. found promoted biogenesis respiration expression of molecules like leptin, adiponectin, matrix metalloproteinases, lipocalin 2, thyroid responsive protein was SIRT1-dependent. Independent validation the proteomics dataset uncovered SIRT1-dependence SREBF1c PPARα signaling adipocytes. nicotinamide mononucleotide acetyltransferase 2 (NMNAT2) during differentiation constitutively repressed NMNAT1 3 levels. Supplementing with booster (NMN) increased levels SIRT1, PGC-1α its transcriptional targets, reduced pro-fibrotic collagens (Col6A1 Col6A3) a SIRT1-dependent manner. Investigating impact functional interaction insights into how metabolism modulates could potentially lead new avenues developing therapeutics for obesity

Language: Английский

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Bacteroides uniformis combined with fiber amplifies metabolic and immune benefits in obese mice

Gut Microbes, Journal Year: 2021, Volume and Issue: 13(1), P. 1 - 20

Published: Jan. 1, 2021

Gut microbiota represents a therapeutic target for obesity. We hypothesize that B. uniformis CECT 7771 combined with wheat bran extract (WBE), its preferred carbon source, may exert superior anti-obesity effects. performed 17-week intervention in diet-induced obese mice receiving either uniformis, WBE, or their combination to identify interactions and independent actions on metabolism immunity. WBE was the most effective intervention, curbing weight gain adiposity, while exerting more modest effects separately. The restored insulin-dependent metabolic routes fat liver, although bacterium primary driver improving whole-body glucose disposal. Moreover, uniformis-combined caused highest increases butyrate proportion of induced intraepithelial lymphocytes type-3 innate lymphoid cells intestinal epithelium. Thus, strengthening first line immune defense against unhealthy diets associated dysbiosis intestine. This also attenuated altered IL22 signaling liver inflammation. Our study shows opportunities employing aid treatment

Language: Английский

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UCP1 governs liver extracellular succinate and inflammatory pathogenesis

Nature Metabolism, Journal Year: 2021, Volume and Issue: 3(5), P. 604 - 617

Published: May 17, 2021

Language: Английский

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Time-restricted feeding mitigates obesity through adipocyte thermogenesis

Science, Journal Year: 2022, Volume and Issue: 378(6617), P. 276 - 284

Published: Oct. 20, 2022

Misalignment of feeding rhythms with the light-dark cycle leads to disrupted peripheral circadian clocks and obesity. Conversely, restricting active period mitigates metabolic syndrome through mechanisms that remain unknown. We found genetic enhancement adipocyte thermogenesis ablation zinc finger protein 423 (ZFP423) attenuated obesity caused by consumption a high-fat diet during inactive (light) increasing futile creatine cycling in mice. Circadian control metabolism underlies timing diet-induced thermogenesis, overexpression clock activator brain muscle Arnt-like protein-1 (BMAL1) ameliorated complications These findings uncover rhythmic creatine-mediated as an essential mechanism drives benefits time-restricted feeding.

Language: Английский

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Adipose tissue at single-cell resolution

Cell Metabolism, Journal Year: 2023, Volume and Issue: 35(3), P. 386 - 413

Published: March 1, 2023

Language: Английский

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The promise of new anti-obesity therapies arising from knowledge of genetic obesity traits

Nature Reviews Endocrinology, Journal Year: 2022, Volume and Issue: 18(10), P. 623 - 637

Published: July 28, 2022

Language: Английский

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Triglyceride cycling enables modification of stored fatty acids

Nature Metabolism, Journal Year: 2023, Volume and Issue: 5(4), P. 699 - 709

Published: April 3, 2023

Triglyceride cycling is the process of continuous degradation and re-synthesis triglyceride in cellular stores. We show 3T3-L1 adipocytes that triglycerides are subject to rapid turnover re-arrangement fatty acids with an estimated half-life 2-4 h. develop a tracing technology can simultaneously quantitatively follow metabolism multiple study futile substrate cycle directly molecular species resolution. Our approach based on alkyne acid tracers mass spectrometry. The connected modification released by elongation desaturation. Through modification, saturated slowly converted monounsaturated acids, linoleic arachidonic acid. conclude renders stored accessible for metabolic alteration. overall facilitates adjustments pool meet changing needs cell.

Language: Английский

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An insight into brown/beige adipose tissue whitening, a metabolic complication of obesity with the multifactorial origin

Frontiers in Endocrinology, Journal Year: 2023, Volume and Issue: 14

Published: Feb. 16, 2023

Brown adipose tissue (BAT), a thermoregulatory organ known to promote energy expenditure, has been extensively studied as potential avenue combat obesity. Although BAT is the opposite of white (WAT) which responsible for storage, shares thermogenic capacity with beige that emerges from WAT depots. This unsurprising both and display huge difference in terms their secretory profile physiological role. In obesity, content declines these tissues acquire characteristics via process called “whitening”. rarely explored its implication whether it contributes or exacerbates Emerging research demonstrated BAT/beige whitening sophisticated metabolic complication obesity linked multiple factors. The current review provides clarification on influence various factors such diet, age, genetics, thermoneutrality, chemical exposure whitening. Moreover, defects mechanisms underpin are described. Notably, can be marked by accumulation large unilocular lipid droplets, mitochondrial degeneration, collapsed capacity, virtue dysfunction, devascularization, autophagy, inflammation.

Language: Английский

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Adipose Tissue and Metabolic Health

Diabetes & Metabolism Journal, Journal Year: 2023, Volume and Issue: 47(5), P. 595 - 611

Published: Sept. 26, 2023

In this review, we provide a brief synopsis of the connections between adipose tissue and metabolic health highlight some recent developments in understanding exploiting adipocyte biology. Adipose plays critical roles regulation systemic glucose lipid metabolism secretes bioactive molecules possessing endocrine, paracrine, autocrine functions. Dysfunctional has detrimental impact on is intimately involved key aspects diseases such as insulin resistance, overload, inflammation, organelle stress. Differences distribution fat depots characteristics relate to divergent degrees dysfunction found metabolically healthy unhealthy obese individuals. Thermogenic adipocytes increase energy expenditure via mitochondrial uncoupling or adenosine triphosphate-consuming futile substrate cycles, while functioning sink participating crosstalk with other organs. Manipulation provides wealth opportunities intervene combat progression associated diseases. We discuss current treatment modalities for obesity including incretin hormone analogs touch upon emerging strategies therapeutic potential exosome-based therapy, pharmacological activation brown beige thermogenesis, administration inhibition adipocyte-derived factors.

Language: Английский

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