Malfunction of adipose mitochondria and the development of obesity and T2Diabetes

· TGI - General, TGI - Health

Excess of adipose tissue is accompanied by an increase in the risk of developing insulin resistance, type 2 diabetes (T2D) and other complications. Nevertheless, total or partial absence of fat or its accumulation in other tissues (lipotoxicity) is also associated to these complications.

Brown adipose tissue (BAT) is considered as a thermogenic adipose tissue with higher oxidative capacityWhite adipose tissue (WAT) was traditionally considered a metabolically active storage tissue for lipids, but nowadays, WAT is also considered an endocrine organ that contributes to energy homeostasis.

Model of origin of adipocytes in different fat depots. Progenitor cells derived from mesenchimal stem cells may yield progenitor cells expressing or not Myf5 (Myf5+ or Myf5−). The Myf5+ progenitor cells may differentiate into brown adipocytes or into myotubes. Myf5− progenitor cells may differentiate into preadipocytes, which may differentiate into white preadipocytes and then in mature white adipocytes. There are inducible brown adipocytes in subcutaneous WAT that are not derived from Myf5+ progenitor cells, which origin is under discussion: from brown preadipocytes or from trans-differentiation of matures white adipocytes. Mitochondrias are present in preadipocytes and mature adipocytes in both WAT and BAT.

Experimental evidence tends to link the malfunction of adipose mitochondria with the development of obesity and T2D.

This article by Gema Medina-Gómez, discusses the importance of mitochondrial function in adipocyte biology and the increased evidences of mitochondria dysfunction in these epidemics.

Mitochondrial functions in adipocytes from WAT and BAT. In adipocytes, pyruvate derived form glucose by glycolysis is converted into acetyl-CoA in the matrix. Alternatively, fatty acids from lipolysis can be taken into the mitochondrial matrix and be oxidized to acetyl-CoA through the fatty acid β-oxidation. The acetyl groups are oxidized via the TCA cycle. The electrons derived form oxido–reduction reactions are finally accepted by O2. The energy retrieved from electrochemical proton gradient in the respiratory chain is used for ATP synthesis. However, in brown adipocytes, UCP-1 uncouples the respiratory chain of ATP production, converting the metabolic energy in heat. The activity of transcription factors is turn on during both processes of adipogenesis and mitochondrial biogenesis in WAT and BAT.

New strategies targeting adipocyte mitochondria from WAT and BAT are also discussed as therapies against obesity and its complications in the near future.



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