Mitochondrial development and the influence of its dysfunction during rat adipocyte differentiation

Abstract

Mitochondrial biogenesis is inherent to adipocyte differentiation. Mitochondrial dysfunction leads to abnormal lipid accumulation or the deterioration of the differentiation process. The aim of this study is to investigate the mitochondrial development during the differentiation of rat primary adipocytes and the effect of mitochondrial dysfunction on this process. We found, for the first time, that the number of mitochondria markedly increased during adipocyte differentiation by transmission electron microscopy. By immunofluorescence staining that the protein content of Cyt c increased in differentiated adipocyte in comparison with preadipocyte. The mRNA expression levels of mitochondrial gene including cytochromes c (Cyt c), malate dehydrogenases (MDH), and peroxisome proliferator activated receptor (PPAR) gamma coactivator-1beta (PGC-1beta) significantly increased along with the proceeding of adipocyte differentiation. The damage to mitochondrial respiratory chain function by rotenone caused significant decrease in gene expressions including mitochondrial MDH and PGC-1beta, and PPARgamma, CAAT/enhancer binding protein alpha (C/EBPalpha) and sterol regulatory element binding protein-1c (SREBP-1c), which are known as transcription factors of differentiation, and differentiation marker gene named fatty acid synthetase. Moreover, an apparent decrease was found in the synthesis of triglyceride and ATP due to the damage to mitochondria by rotenone. Based on the above results, our present study revealed that the density and oxidative capacity of mitochondrial markedly increased during primary adipocyte differentiation, and on the other hand, we suggested that mitochondria dysfunction might inhibit the differentiation process.

Prohibitin Overexpression in Adipocytes Induces Mitochondrial Biogenesis, Leads to Obesity Development, and Affects Glucose Homeostasis in a Sex-Specific Manner

“…The obese phenotype of Mito-Ob mice affirms the emerging notion that PHB and adipocyte mitochondria play a role in the regulation of adipose tissue homeostasis and metabolic regulation (1)(2)(3)(4)(8)(9)(10). However, the metabolic consequences of obesity in Mito-Ob mice are sex specific, suggesting that intrinsic differences exist in the way adipose tissues are regulated and/or respond to obesity development in male and female mice despite a similar underlying cause.…”

“…Mitochondrial biogenesis is an important process in adipocyte differentiation (2,3). However, the role of adipocyte mitochondria in adipose tissue homeostasis and metabolic regulation is not entirely understood.…”

Mesodermal developmental gene Tbx15 impairs adipocyte differentiation and mitochondrial respiration

“…The role of Tbx15 in regulating mitochondrial function in adipocytes is consistent with the lower mitochondrial respiration observed in s.c. preadipocytes compared with intraabdominal perigonadal preadipocytes. This role of mitochondrial respiration in adipocyte function appears to be biphasic-complete inhibition of mitochondrial respiration by rotenone in preadipocytes can increase triglyceride accumulation without inducing differentiation (33), whereas partial inhibition of mitochondrial respiration during preadipocyte differentiation decreases the ability of these cells to differentiate and store triglycerides (34). By comparison, overexpression of Tbx15 in 3T3-L1 preadipocytes causes a moderate decrease in mitochondrial respiration and mitochondrial mass, which results in impaired adipocyte differentiation capacity and reduced triglyceride accumulation.…”

“…*P < 0.05. against obesity (37), suggesting that increased mitochondrial respiration in WAT decreases adipocyte fat content. However, mitochondrial dysfunction in preadipocytes inhibits adipocyte differentiation and subsequently triglyceride accumulation in vitro (34). Interestingly, the nucleoside reverse transcriptase inhibitors, which induce lipodystrophies in some patients being treated for HIV-1, decrease mitochondrial activity and lipid content in cell culture (38).…”

Opposite effects of 17-β estradiol and testosterone on mitochondrial biogenesis and adiponectin synthesis in white adipocytes

“…Adiponectin also exerts autocrine effects in WAT, promoting adipocyte differentiation through the activation of peroxisome proliferator-activated receptor g (PPARg), a key transcriptional factor to initiate and maintain the fully differentiated adipocyte phenotype (Spiegelman et al 1993, Fu et al 2005. Mitochondrial function is an important factor in adipocyte differentiation (Lu et al 2010), and an impairment of mitochondrial function has been related to alterations in adipokine synthesis, including adiponectin, in WAT (Koh et al 2007, Wang et al 2013.…”