The role of adiponectin in the circadian regulation of insulin sensitivity

Project Description:

Obesity and diabetes are major threats to public health and have reached epidemic proportions throughout the world [1]. Numerous epidemiological studies report that the risk of developing obesity and type-2 diabetes (T2D) is enhanced by lifestyle factors such as circadian misalignment [2–4]. Mammals harbor a ubiquitous circadian clock system with a master pacemaker located in the hypothalamic suprachiasmatic nucleus (SCN). Like the central clock in the SCN, peripheral functional clocks have been described in various tissues [2,5]. Noteworthy, liver circadian clocks play a pivotal role in energy metabolism, partly through regulation of glucose hemostasis and hepatic insulin sensitivity [6]. Adiponectin is a circulating adipose tissue-derived hormone enhancing insulin sensitivity in target tissues by suppressing hepatic gluconeogenesis and increasing fatty acid oxidation [7]. Recent studies from our lab have shown that adiponectin can reset clocks in the mediobasal hypothalamus (MBH) [8]. However, it is currently unknown whether it has similar effects on liver circadian clock. It is widely accepted that adipose adiponectin manipulates insulin signaling [9]. However, in the context of the circadian clock, whether adiponectin exerts its effect on insulin sensitivity through liver clock resetting still needs to be determined. Based on the above discussion, we hypothesize that adiponectin conveys circadian regulation of insulin sensitivity in the liver. In turn, rhythmic adiponectin administration might restore insulin signaling or insulin sensitivity in diet-induced obesity/insulin resistance.

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