Adiponectin promotes adipocyte differentiation, insulin sensitivity, and lipid accumulation

Abstract

Adiponectin is secreted from adipocytes, and low circulating levels have been epidemiologically associated with obesity, insulin resistance, type 2 diabetes, and cardiovascular disease. To investigate whether adiponectin could exert autocrine effects in adipocytes, we expressed the adiponectin gene in 3T3-L1 fibroblasts. We observed that 3T3-L1 fibroblasts expressing adiponectin have a fast growth phase and reach confluence more rapidly compared with control cells or LacZtransduced cells. Furthermore, cells with overexpressed adiponectin were observed to differentiate into adipocytes more rapidly, and during adipogenesis, they exhibited more prolonged and robust gene expression for related transcriptional factors, CCAAT/enhancer binding protein ␣ (C/EBP2), peroxisome proliferator-activated receptor ␥ (PPAR ␥ ), and adipocyte determination and differentiation factor 1/sterol-regulatory element binding protein 1c (ADD1/SREBP1c) and earlier suppression of PPAR ␥ coactivator-1 ␣ (PGC-1 ␣ ). In fully differentiated adipocytes, adiponectin-overexpressing cells accumulated more and larger lipid droplets compared with control cells. Also, adiponectin increased insulin's ability to maximally stimulate glucose uptake by 78% through increased glucose transporter 4 (GLUT4) gene expression and increased GLUT4 recruitment to the plasma membrane. These data suggest a new role for adiponectin as an autocrine factor in adipose tissues: promoting cell proliferation and differentiation from preadipocytes into adipocytes, augmenting programmed gene expression responsible for adipogenesis, and increasing lipid content and insulin responsiveness of the glucose transport system in adipocytes.

Promoter adiponectin polymorphisms and waist/hip ratio variation in a prospective French adults study

“…Bouatia-Naji et al 18 suggested the physiological contribution of adiponectin to weight gain over time may be mediated by its insulin-sensitizing action in adipose tissue. Indeed, Fu et al 29 suggested a new role for adiponectin as a factor augmenting programmed gene expression responsible for adipogenesis (that is, PPARg) and increasing lipid content and insulin responsiveness of the glucose transport system in adipocytes.…”

Association of adiponectin polymorphism with cord blood adiponectin concentrations and intrauterine growth

“…First, in the second half of intrauterine life, fetal adipose tissue rapidly expands with increasing size and number of adipocytes, and is mainly composed of small newly differentiated adipocytes, which secrete more adiponectin to increase adipocyte proliferation and lipid accumulation. 33,38 Additionally, a negative feedback on adiponectin production caused by fat mass with hypertrophic adipocytes has not been found in newborns. Although further investigations are needed, the genetic effects of rs266729 SNP on adiponectin promoter activity is likely to alter adipose tissue metabolism in intrauterine life, unlike in adults.…”

Relationship between adiponectin, obesity and insulin resistance

“…Thus, adiponectin promotes adipocyte differentiation and increased insulin sensitivity. 15,16 Also, recent in vivo and in vitro studies provided evidence of a regulatory feedback loop by which adiponectin controls its own production and the expression of its receptor. In addition to the regulatory capacity, adiponectin acts as an autocrine and paracrine factor to inhibit the secretion by adipocytes of interleukins 6 and 8, macrophage inflammatory protein 1α/β and monocyte chemotactic protein-1, which, in turn, can inhibit the storage of lipids and insulin sensitivity in adipocytes.…”