GH Does Not Modulate the Early Fasting-Induced Release of Free Fatty Acids in Mice

Abstract

Fasting results in the mobilization of adipose stores and the elevation of levels of free fatty acids (FFA). In humans, this process is driven by a release in GH. Little is known regarding the role of GH in modulating this process during early stages of fasting in the mouse. Confirmation of the role of GH in modulating FFA release in the fasting mouse is of particular importance given the frequent use of mouse models to study metabolic mechanisms. Here, we correlate the initial release of FFA throughout fasting in mice with pulsatile GH secretion. Observations illustrate the rapid release of FFA in response to food withdrawal. This does not correlate with a rise in GH secretion. Rather, we observed a striking loss in pulsatile secretion of GH throughout the first 6 h of fasting, suggesting that GH does not modulate the initial release of FFA in the mouse in response to fasting. This was confirmed in GH receptor knockout mice, in which we observed a robust fasting-induced rise in FFA. We further illustrate the dynamic relationship between the orexigenic and anorexigenic hormones ghrelin and leptin during fasting in the mouse. Our findings show an initial suppression of leptin and the eventual rise in circulating levels of acyl-ghrelin with fasting. However, altered acyl-ghrelin and leptin secretion occurs well after the rise in FFA and the suppression of GH secretion. Consequently, we conclude that although acyl-ghrelin and leptin may modulate the physiological response to drive food intake, these changes do not contribute to the initial loss of pulsatile GH secretion. Rather, it appears that the suppression of GH secretion in fasting may occur in response to an elevation in fasting levels of FFA or physiological stress. Observations highlight a divergent role for GH in modulating FFA release between man and mouse.

A Single Bout of Fasting (24 h) Reduces Basal Cytokine Expression and Minimally Impacts the Sterile Inflammatory Response in the White Adipose Tissue of Normal Weight F344 Rats

“…Corroborating previous reports, a 24 h fast significantly reduced body weight [34] and altered systemic markers of fed status including plasma glucose, NEFA, insulin, and leptin [21, 22, 35, 36]. This study further demonstrates that a 24 h fast is sufficient to reduce cytokine expression in the blood and WAT under nonstressed conditions.…”

Somatostatin Is Essential for the Sexual Dimorphism of GH Secretion, Corticosteroid-Binding Globulin Production, and Corticosterone Levels in Mice

“…Intrinsic to this method is frequent handling of the mice during bleeding, which is likely to activate the stress response. Although the handling stress was claimed to be negligible, reported corticosterone levels were relatively high at 370 ng/mL (51). Thus, our automated method has the advantage of obtaining serial blood samples from individual mice for extended periods of time during the day or night for the analysis of hormone patterns in the absence of activating the stress axis.…”

Glucose and Fat Metabolism in Acromegaly: From Mice Models to Patient Care

“…First, it is likely that species-specific differences exist regarding the metabolic effects of GH; for instance, one study observed that GH does not modulate the initial release of FFA during fasting in the mouse [82]. Likewise, the epididymal fat pad, which has been most commonly used for mouse studies, has no clinical equivalent, requiring one to use caution in interpreting the clinical relevance of these studies.…”