Characterization of adipocytes derived from fibro/adipogenic progenitors resident in human skeletal muscle.

A population of fibro/adipogenic but non-myogenic progenitors located between skeletal muscle fibers was recently discovered. The aim of this study was to determine the extent to which these progenitors differentiate into fully functional adipocytes. The characterization of muscle progenitor-derived adipocytes is a central issue in understanding muscle homeostasis.

Hypoxia inhibits Cavin-1 and Cavin-2 expression and down-regulates caveolae in adipocytes.

During obesity, a hypoxic state develops within the adipose tissue, resulting in insulin resistance. To understand the underlying mechanism, we analyzed the involvement of caveolae because they play a crucial role in the activation of insulin receptors. In the present study, we demonstrate that in 3T3-L1 adipocytes, hypoxia induces the disappearance of caveolae and inhibits the expression of Cavin-1 and Cavin-2, two proteins necessary for the formation of caveolae.

Regulated in development and DNA damage responses -1 (REDD1) protein contributes to insulin signaling pathway in adipocytes.

REDD1 (Regulated in development and DNA damage response 1) is a hypoxia and stress response gene and is a negative regulator of mTORC1. Since mTORC1 is involved in the negative feedback loop of insulin signaling, we have studied the role of REDD1 on insulin signaling pathway and its regulation by insulin. In human and murine adipocytes, insulin transiently stimulates REDD1 expression through a MEK dependent pathway.

Insulin induces REDD1 expression through hypoxia-inducible factor 1 activation in adipocytes.

REDD1 (regulated in development and DNA damage responses) is essential for the inhibition of mTORC1 (mammalian target of rapamycin complex) signaling pathway in response to hypoxia. REDD1 expression is regulated by many stresses such as hypoxia, oxidative stress, and energy depletion. However, the regulation of REDD1 expression in response to insulin remains unknown.

GLUT4 molecules are recruited at random for insertion within the plasma membrane upon insulin stimulation.

Glucose transporter 4 (GLUT4) is efficiently retained intracellularly. Here, we investigated the insulin-induced reduction of retention. While increasing insulin concentrations led to gradual increases in both the amount of recycling GLUT4 molecules and cell surface GLUT4 levels, the kinetics of the increase in time was independent of insulin concentration.

Hypoxia decreases insulin signaling pathways in adipocytes.

Objective: Obesity is characterized by an overgrowth of adipose tissue that leads to the formation of hypoxic areas within this tissue. We investigated whether this phenomenon could be responsible for insulin resistance by studying the effect of hypoxia on the insulin signaling pathway in adipocytes.

Research Design And Methods: The hypoxic signaling pathway was modulated in adipocytes from human and murine origins through incubation under hypoxic conditions (1% O(2)) or modulation of hypoxia-inducible factor (HIF) expression.