Proteome Imbalance of Mitochondrial Electron Transport Chain in Brown Adipocytes Leads to Metabolic Benefits.

@article{Masand2018ProteomeIO,
  title={Proteome Imbalance of Mitochondrial Electron Transport Chain in Brown Adipocytes Leads to Metabolic Benefits.},
  author={Ruchi Masand and E. Paulo and Dongmei Wu and Yangmeng Wang and D. Swaney and D. Jimenez-Morales and N. Krogan and Biao Wang},
  journal={Cell metabolism},
  year={2018},
  volume={27 3},
  pages={
          616-629.e4
        }
}
Brown adipose tissue (BAT) thermogenesis is critical for thermoregulation and contributes to total energy expenditure. However, whether BAT has non-thermogenic functions is largely unknown. Here, we describe that BAT-specific liver kinase b1 knockout (Lkb1BKO) mice exhibited impaired BAT mitochondrial respiration and thermogenesis but reduced adiposity and liver triglyceride accumulation under high-fat-diet feeding at room temperature. Importantly, these metabolic benefits were also present in… Expand
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References

SHOWING 1-10 OF 68 REFERENCES
Lack of Adipocyte AMPK Exacerbates Insulin Resistance and Hepatic Steatosis through Brown and Beige Adipose Tissue Function.
TLDR
In response to a high-fat diet, iβ1β2AKO mice more rapidly developed liver steatosis as well as glucose and insulin intolerance, and AMPK in adipocytes is vital for maintaining mitochondrial integrity, responding to pharmacological agents and thermal stress, and protecting against nutrient-overload-induced NAFLD and insulin resistance. Expand
Histone Deacetylase 3 Prepares Brown Adipose Tissue For Acute Thermogenic Challenge
TLDR
It is shown that histone deacetylase 3 (HDAC3) is required to activate brown adipose tissue enhancers to ensure thermogenic aptitude and uniquely primes UCP1 and the thermogenic transcriptional program to maintain a critical capacity for thermogenesis in brown adiposes tissue that can be rapidly engaged upon exposure to dangerously cold temperature. Expand
Lkb1 controls brown adipose tissue growth and thermogenesis by regulating the intracellular localization of CRTC3
TLDR
In conclusion, it is suggested that inhibition of Lkb1 or its downstream signalling in adipocytes could be a novel strategy to increase energy expenditure in the context of obesity, diabetes and other metabolic diseases. Expand
Adipose-Specific Deficiency of Fumarate Hydratase in Mice Protects Against Obesity, Hepatic Steatosis, and Insulin Resistance
TLDR
Results show that under the cold stress of regular animal room conditions, adipocyte-specific FH deficiency in mice causes mitochondrial energy depletion in adipose tissues and protects from obesity, hepatic steatosis, and insulin resistance, suggesting that in cold-stressed animals, mitochondrial function in adipOSE tissue is a determinant of fat mass and insulin sensitivity. Expand
Adipose fatty acid oxidation is required for thermogenesis and potentiates oxidative stress-induced inflammation.
TLDR
It is shown that fatty acid oxidation is required for cold-induced thermogenesis in BAT and high-fat diet-induced oxidative stress and inflammation in visceral white adipose tissue (WAT); however, high- fat diet- induced glucose intolerance was not improved. Expand
Loss of Adipose Fatty Acid Oxidation Does Not Potentiate Obesity at Thermoneutrality.
TLDR
Although the loss of adipose fatty acid oxidation resulted in clear molecular, cellular, and physiologic deficits in BAT, body weight gain and glucose tolerance were similar in control and Cpt2(A-/-) mice in response to a high-fat diet, even when mice were housed at thermoneutrality. Expand
Desnutrin/ATGL is regulated by AMPK and is required for a brown adipose phenotype.
TLDR
Overall, desnutrin is phosphorylated/activated by AMPK to increase lipolysis and brings FA oxidation and UCP-1 induction for thermogenesis and despite adiposity and impaired BAT function, desnutsrin-ASKO mice have improved hepatic insulin sensitivity with lower DAG levels. Expand
UCP1 in brite/beige adipose tissue mitochondria is functionally thermogenic.
TLDR
It was found that, in mitochondria isolated from the inguinal "white" adipose depot of cold-acclimated mice, UCP1 protein levels almost reached those in brown-fat mitochondria, indicating that the classical brown adipose tissue depots would still predominate in thermogenesis. Expand
Mice lacking mitochondrial uncoupling protein are cold-sensitive but not obese
TLDR
The role of UCP in the regulation of body mass is determined by targeted inactivation of the gene encoding it by finding that UCP-deficient mice consume less oxygen after treatment with a β3-adrenergic-receptor agonist and are sensitive to cold, indicating that their thermo-regulation is defective. Expand
Adipose tissue mitochondrial dysfunction triggers a lipodystrophic syndrome with insulin resistance, hepatosteatosis, and cardiovascular complications
  • C. Vernochet, F. Damilano, +6 authors C. Kahn
  • Biology, Medicine
  • FASEB journal : official publication of the Federation of American Societies for Experimental Biology
  • 2014
Mitochondrial dysfunction in adipose tissue occurs in obesity, type 2 diabetes, and some forms of lipodystrophy, but whether this dysfunction contributes to or is the result of these disorders isExpand
...
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4
5
...