Metformin Inhibits Lipid Droplets Fusion and Growth via Reduction in Cidec and Its Regulatory Factors in Rat Adipose-Derived Stem Cells

Abstract

Metformin is still being investigated due to its potential use as a therapeutic agent for managing overweight or obesity. However, the underlying mechanisms are not fully understood. Inhibiting the adipogenesis of adipocyte precursors may be a new therapeutic opportunity for obesity treatments. It is still not fully elucidated whether adipogenesis is also involved in the weight loss mechanisms by metformin. We therefore used adipose-derived stem cells (ADSCs) from inguinal and epididymal fat pads to investigate the effects and mechanisms of metformin on adipogenesis in vitro. Our results demonstrate the similar effect of metformin inhibition on lipid accumulation, lipid droplets fusion, and growth in adipose-derived stem cells from epididymal fat pads (Epi-ADSCs) and adipose-derived stem cells from inguinal fat pads (Ing-ADSCs) cultures. We identified that cell death-inducing DFFA-like effector c (Cidec), Perilipin1, and ras-related protein 8a (Rab8a) expression increased ADSCs differentiation. In addition, we found that metformin inhibits lipid droplets fusion and growth by decreasing the expression of Cidec, Perilipin1, and Rab8a. Activation of AMPK pathway signaling in part involves metformin inhibition on Cidec, Perilipin1, and Rab8a expression. Collectively, our study reveals that metformin inhibits lipid storage, fusion, and growth of lipid droplets via reduction in Cidec and its regulatory factors in ADSCs cultures. Our study supports the development of clinical trials on metformin-based therapy for patients with overweight and obesity.

Immunostimulatory and anti‑obesity activities of Adenocaulon himalaicum leaves in RAW264.7 and 3T3‑L1 cells

“…Obesity can be prevented by regulating the various molecules involved in lipid accumulation in adipocytes. The first treatment for obesity is the inhibition of adipogenesis, which is the process by which preadipocytes differentiate into mature adipocytes ( 22 ). A number of anti-obesity agents that inhibit adipogenesis have been developed ( 22 ).…”

“…The first treatment for obesity is the inhibition of adipogenesis, which is the process by which preadipocytes differentiate into mature adipocytes ( 22 ). A number of anti-obesity agents that inhibit adipogenesis have been developed ( 22 ). The present study confirmed that AHL effectively reduced the protein levels of CEBPα and PPARγ in 3T3-L1 cells.…”

Decreased expression of ATP‐binding cassette protein G1 promotes abnormal adipogenesis of condylar chondrocytes in temporomandibular joint osteoarthritis

“…Changes in the expression of ABCG1 in condylar chondrocytes did not affect the expression of Cebpα and Fabp4, indicating that lipid biosynthesis and outflow to the outside of the condylar chondrocytes are two relatively independent processes, and abnormal biological forces may affect these two processes. Adiponectin and Perilipin1 are closely related to the content of mature lipid droplets formed in cells 44 . Therefore, when ABCG1 in condylar chondrocytes is inhibited or overexpressed, the amount of lipid accumulation in cells is directly affected, thereby affecting the expression of Adiponectin and Perilipin1.…”

Inhibition of lipid droplet accumulation by Solanum nigrum by suppressing adipogenesis and inducing lipolysis, thermogenesis and autophagy in 3T3‑L1 cells

“…Obesity occurs when there is excessive accumulation of fat in adipose tissue ( 13 ). White adipose tissue (WAT) is known to increase because of excessive lipid accumulation within adipocytes, which is a major characteristic of obesity ( 14 ). Adipogenesis, the process by which preadipocytes differentiate into mature adipocytes, increases the number of mature adipocytes in WAT ( 15-17 ).…”