Molecular Mechanisms of Adipogenesis: The Anti-adipogenic Role of AMP-Activated Protein Kinase

Abstract

Obesity is now a widespread disorder, and its prevalence has become a critical concern worldwide, due to its association with common co-morbidities like cancer, cardiovascular diseases and diabetes. Adipose tissue is an endocrine organ and therefore plays a critical role in the survival of an individual, but its dysfunction or excess is directly linked to obesity. The journey from multipotent mesenchymal stem cells to the formation of mature adipocytes is a well-orchestrated program which requires the expression of several genes, their transcriptional factors, and signaling intermediates from numerous pathways. Understanding all the intricacies of adipogenesis is vital if we are to counter the current epidemic of obesity because the limited understanding of these intricacies is the main barrier to the development of potent therapeutic strategies against obesity. In particular, AMP-Activated Protein Kinase (AMPK) plays a crucial role in regulating adipogenesis -it is arguably the central cellular energy regulation protein of the body. Since AMPK promotes the development of brown adipose tissue over that of white adipose tissue, special attention has been given to its role in adipose tissue development in recent years. In this review, we describe the molecular mechanisms involved in adipogenesis, the role of signaling pathways and the substantial role of activated AMPK in the inhibition of adiposity, concluding with observations which will support the development of novel chemotherapies against obesity epidemics.

Effect and Comparison of Luteolin and Its Derivative Sodium Luteolin‐4′‐sulfonate on Adipogenic Differentiation of Human Bone Marrow‐Derived Mesenchymal Stem Cells through AMPK‐Mediated PPARγ Signaling

“…On the other hand, luteolin-OSO 3 Na treatment slightly increased AMPK phosphorylation, however not comparable to luteolin. These results were parallel to MAPK activation as reports had shown that activation of p38, ERK, and JNK MAPKs during adipogenesis was in the opposite manner with AMPK activation [ 15 , 23 ]. Effect of samples on MAPK activation was further analyzed by flow cytometry assessing the expression of phosphorylated MAPK (ERK1/2) in adipo-induced hBM-MSCs.…”

“…Results suggested that luteolin inhibited the adipogenesis in hBM-MSCs via downregulation of MAPKs. MAPK-linked adipogenesis inducement occurs along with downregulated AMPK activation [ 23 ]. In this context, the effect of luteolin and luteolin-OSO 3 Na on AMPK activation was also analyzed by western blotting.…”

Cudratricusxanthone A Inhibits Lipid Accumulation and Expression of Inducible Nitric Oxide Synthase in 3T3-L1 Preadipocytes

“…AMPK is a heterotrimeric protein complex that is composed of α, β, and γ subunits [ 34 ], and plays a key role in cellular energy homeostasis [ 35 ]. There is much evidence that activation of AMPK inhibits lipid accumulation (adipogenesis) in 3T3-L1 preadipocyte differentiation [ 36 ]. The α subunit of AMPK (AMPKα) contains its catalytic domain where AMPK becomes activated when phosphorylation takes place at T172 [ 37 , 38 , 39 ].…”

Sinensol-C Isolated from Spiranthes sinensis Inhibits Adipogenesis in 3T3-L1 Cells through the Regulation of Adipogenic Transcription Factors and AMPK Activation

“…Several studies have identified AMPK activation as a target for the treatment of obesity [ 52 , 53 ]. Accumulating evidence suggests that activation of the AMPK pathway suppressed PPARγ, C/EBPα, and SREBP-1c expression, and thus inhibits lipid accumulation during adipogenesis [ 54 , 55 , 56 ]. In addition, studies have related AMPK activation with the level of adiponectin [ 47 , 57 , 58 , 59 ].…”