While it is well established that obesity causes insulin resistance, much less is known about how obesity modifies other hormonal signaling pathways. Several studies have indicated that in addition to the suppression of anabolic actions of insulin, there is a coordinate activation of catabolic pathways in obesity (Ravussin et al. 2014). While growth hormone is not generally thought of as catabolic, it does mobilize fatty acids for growth and energy and is a key counter-regulatory hormone to insulin during fasting. In this work, Hogild et al. evaluate growth hormone signaling in human subjects and ask whether this could be moderated by obesity. They show that GH levels in response to fasting are attenuated in obesity. While GH produced similar increases in lipolysis in the lean and obese subjects, they only observed elevated endogenous glucose production in the obese subjects, potentially suggesting direct hepatic actions, rather than indirect regulation of gluconeogenesis through lipolysis. More importantly, overall insulin sensitivity and glucose disposal rates were reduced equally in lean and obese individuals after a GH bolus. These data compellingly argue that GH signaling is similar in the lean and obese, and that it’s counter-regulatory role during fasting is less prominent in the obese. Thus GH is unlikely to be the missing catabolic factor associated with obesity.
While it is well established that obesity causes insulin resistance, much less is known about how obesity modifies other hormonal signaling pathways. Several studies have indicated that in addition to the suppression of anabolic actions of insulin, there is a coordinate activation of catabolic pathways in obesity (Ravussin et al. 2014). While growth hormone is not generally thought of as catabolic, it does mobilize fatty acids for growth and energy and is a key counter-regulatory hormone to insulin during fasting. In this work, Hogild et al. evaluate growth hormone signaling in human subjects and ask whether this could be moderated by obesity. They show that GH levels in response to fasting are attenuated in obesity. While GH produced similar increases in lipolysis in the lean and obese subjects, they only observed elevated endogenous glucose production in the obese subjects, potentially suggesting direct hepatic actions, rather than indirect regulation of gluconeogenesis through lipolysis. More importantly, overall insulin sensitivity and glucose disposal rates were reduced equally in lean and obese individuals after a GH bolus. These data compellingly argue that GH signaling is similar in the lean and obese, and that it’s counter-regulatory role during fasting is less prominent in the obese. Thus GH is unlikely to be the missing catabolic factor associated with obesity.
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