Mitochondrial Pyruvate Carriers are not Required for Adipogenesis but are Regulated by High‐Fat Feeding in Brown Adipose Tissue

Abstract

Original Article OBESITY BIOLOGY AND INTEGRATED PHYSIOLOGY Study ImportanceWhat is already known?► Mitochondrial pyruvate carriers (MPCs) are essential for pyruvate to be transported into the mitochondria and utilized as substrate by the pyruvate dehydrogenase complex for energy production. What does this study add?► This study is novel because it demonstrates that MPCs are not required for the adipogenesis of 3T3-L1 cells, suggesting that other substrates may compensate for energy production during in vitro adipogenesis. ► This study is also novel because it shows that MPCs are regulated by diet-induced obesity in brown adipose tissue.Objective: The objectives of this study were to assess the role of mitochondrial pyruvate carriers (MPCs) in adipocyte development in vitro and determine whether MPCs are regulated in vivo by high-fat feeding in male and female C57BL/6J mice.Methods: This study utilized small interfering RNA-mediated knockdown to assess the requirement of MPC1 for adipogenesis in the 3T3-L1 model system. Treatment with UK-5099, a potent pharmacological MPC inhibitor, was also used to assess the loss of MPC activity. Western blot analysis was performed on adipose tissue samples from mice on a low-fat diet or a high-fat diet (HFD) for 12 weeks.Results: The loss of MPC expression via small interfering RNA-mediated knockdown or pharmacological inhibition did not affect adipogenesis of 3T3-L1 cells. In vivo studies indicated that expression of MPCs was significantly decreased in brown adipose tissue of male mice, but not female, on an HFD. Conclusions: Although MPCs are essential for pyruvate transport, MPCs are not required for adipogenesis in vitro, suggesting that other substrates can be used for energy production when the MPC complex is not functional. Also, a significant decrease in MPC1 and 2 expression occurred in brown fat, but not white fat, of male mice fed an HFD.Obesity (2020) 28, 293-302.

Substrate Utilization by Brown Adipose Tissue: What’s Hot and What’s Not?

“…Pyruvate, the product of glycolysis, can be converted to acetyl coenzyme A (acetyl-CoA) by pyruvate dehydrogenase (PDH) to feed into the tricarboxylic acid (TCA) cycle. The mitochondrial pyruvate transporters MPC1 and MPC2 are highly expressed in rodent BAT and upregulated by cold exposure (37,38). Furthermore, we found higher expression of the PDH subunit PDHA1 (and a trend for PDHB) in human BAT compared with WAT, in-keeping with conversion of pyruvate to acetyl-CoA in human BAT (12).…”

Obesity and Mitochondrial Function in Children: A case–control study

“…The importance of MPC during adipocyte formation was investigated utilizing two different techniques in a new study. The manifestation and/or activity of MPCs were not necessary for adipogenesis, as established by pharmacological inhibition of MPCs and siRNA-mediated suppression of MPC1 [21].…”

A microneedle patch realizes weight loss through photothermal induction of fat browning

“…We also examined the antiadipogenic effects of NIR-induced PDA-NPs using a modified cocktail induction method (MDIinduced) for the 3T3-L1 adipocyte differentiation paradigm. 34 A revised MDI induction technique was used to induce 3T3-L1 precursor cells to progressively develop into mature white adi-pocytes; the differentiation processes of 3T3-L1 preadipocytes are described in detail in the ESI (Fig. S2 †).…”