No abstract

SUMMARY Adipose tissue is an essential regulator of metabolic homeostasis. In contrast with white adipose tissue, which stores excess energy in the form of triglycerides, brown adipose tissue is thermogenic, dissipating energy as heat via the unique expression of the mitochondrial uncoupling protein UCP1. A subset of UCP1+ adipocytes develop within white adipose tissue in response to physiological stimuli, however, the developmental origin of these “brite” or “beige” adipocytes is unclear. Here, we report the identification of a BMP7-ROCK signaling axis regulating beige adipocyte formation via control of the G-actin-regulated transcriptional coactivator myocardin related transcription factor A, MRTFA. White adipose tissue from MRTFA–/– mice contains more multilocular adipocytes and expresses enhanced levels of brown-selective proteins, including UCP1. MRTFA–/– mice also show improved metabolic profiles and protection from diet-induced obesity and insulin resistance. Our study hence unravels a central pathway driving the development of physiologically functional beige adipocytes.

We examined the effects of insulin and insulin-like growth factor I (IGF-I) on the production of collagen by cultures of human embryonic lung fibroblasts. Insulin at 20 ng/ml increased collagen accumulation by 58% and total protein formation by 18%. At 2 micrograms/ml, insulin increased collagen production by 2- to 3-fold and total protein production by 2-fold. The mRNA levels for alpha 1(I) and alpha 1(III) collagen chains were elevated by insulin compared with untreated control values. IGF-I at 10 ng/ml increased collagen production 2-fold. IGF-I at 100 ng/ml maximally increased collagen production 3-fold. A specific antibody to the IGF-I receptor (alpha IR-3) caused a concentration-related decline in insulin-induced collagen formation. The addition of antibody at 1 micrograms/ml, resulted in 80% inhibition of insulin-induced collagen accumulation. Higher levels of antibody were required to inhibit IGF-I mediated collagen formation. The presence of antibody (alpha IR-3) also blocked fibroblast proliferation stimulated by epidermal growth factor plus insulin. These data show that insulin-induced collagen formation is mediated primarily through an interaction with the IGF-I receptor. The modulation of extracellular matrix production by insulin may influence the repair of tissue injury and the development of the accelerated atherosclerosis that accompanies the diabetic state in humans.