Jianrong Han

Adipogenesis and aging: Does aging make fat go MAD?

In advanced old age, fat depot size declines while lipid is redistributed to muscle, bone marrow, and other tissues. Decreased fat depot size is related to reduced fat cell size and function and impaired differentiation of preadipocytes into fat cells. Reduced differentiation-dependent gene expression results from decreased abundance of the adipogenic transcription factors, CCAAT/enhancer binding alpha (C/EBPalpha) and peroxisome proliferator activated receptor gamma (PPARgamma). Increased expression of anti-adipogenic C/EBP family members contributes, perhaps due to cellular stress response pathway activation with aging. Hence, dysfunctional adipocyte-like cells appear in adipose tissue that are smaller and less insulin responsive than fully differentiated fat cells. Adipogenesis can be restored by overexpressing adipogenic transcription factors in preadipocytes from old animals. Redistribution of lipid to extra-adipose sites with aging could result from loss of lipid storage capacity in fat depots, altered fatty acid handling resulting in lipid accumulation, dysdifferentiation of mesenchymal precursors, such as muscle satellite cells and osteoblast precursors, into a partial adipocyte phenotype, or a combination of these mechanisms. Thus, accumulation of mesenchymal adipocyte-like default (MAD) cells in fat depots, muscle, bone marrow, and elsewhere is a potentially reversible process that could contribute to maldistribution of fat in old age.

Modulation of adipocyte lipogenesis by octanoate: involvement of reactive oxygen species

BackgroundOctanoate is a medium-chain fatty acid (MCFA) that is rich in milk and tropical dietary lipids. It also accounts for 70% of the fatty acids in commercial medium chain triglycerides (MCT). Use of MCT for weight control tracks back to early 1950s and is highlighted by recent clinical trials. The molecular mechanisms of the weight reduction effect remain not completely understood. The findings of significant amounts of MCFA in adipose tissue in MCT-fed animals and humans suggest a direct influence of MCFA on fat cell functions.Methods3T3-L1 adipocytes were treated with octanoate in a high glucose culture medium supplemented with 10% fetal bovine serum and 170 nM insulin. The effects on lipogenesis, fatty acid oxidation, cellular concentration of reactive oxygen species (ROS), and the expression and activity of peroxisome proliferator receptor gamma (PPARγ) and its associated lipogenic genes were assessed. In selected experiments, long-chain fatty acid oleate, PPARγ agonist troglitazone, and antioxidant N-acetylcysteine were used in parallel. Effects of insulin, L-carnitine, and etomoxir on β-oxidation were also measured.Resultsβ-oxidation of octanoate was primarily independent of CPT-I. Treatment with octanoate was linked to an increase in ROS in adipocytes, a decrease in triglyceride synthesis, and reduction of lipogenic gene expression. Co-treatment with troglitazone, N-acetylcysteine, or over-expression of glutathione peroxidase largely reversed the effects of octanoate.ConclusionThese findings suggest that octanoate-mediated inactivation of PPARγ might contribute to the down regulation of lipogenic genes in adipocytes, and ROS appears to be involved as a mediator in this process.

Effects of vanadate on leptin production from isolated rat adipocytes

Vanadium, an important trace element in nutrition, actively affects the metabolic activities on all tissues. This work reports the effects of vanadate on leptin production from adipocytes isolated from normal Sprague-Dawley rats, streptozotocin-induced diabetic rats, Zucker lean, and Zucker fa/fa rats. We found that vanadate stimulates leptin production similar to insulin. The maximum leptin production stimulated by vanadate was slightly higher than that by insulin. Treatment with vanadate or insulin also increased the cellular leptin mRNA levels in a ratio similar to the increase in the protein secretion, suggesting that the regulation is at the transcription level. For adipocytes isolated from both streptozotocin-induced diabetic rats and Zucker fa/fa rats, vanadate was a more potent stimulant than insulin on leptin production. This suggests that vanadate may stimulate leptin production by mechanisms that are independent of insulin receptors.