Decreased Pituitary Growth Hormone Response to Growth Hormone-Releasing Factor in Cafeteria-Fed Rats: Dietary and Obesity Effects

In human obesity as well as in rat obesity models a decrease in spontaneous and stimulated GH secretion has been a constant finding. The presence of a decreased pituitary GH synthesis in diet-induced obese male rats was investigated and its possible relationship with obesity-related changes in peripheral hormones was analyzed. Cafeteriadiet-overfed obese male Wistar rats with body fat percentage above 30% had a significantly decreased pituitary GH mRNA transcript level assessed by both Northern blot and in situ hybridization, and a lower pituitary GH protein level as demonstrated by immunocytochemistry. The GH transcript level correlated negatively with the serum leptin and positively with the IGF-I concentration. No differences in circulating tri-iodothyronine, non-fasting insulin and corticosterone levels were found between overfed and control rats. GH release by cultured pituitary cells from overfed rats was comparable to that by cells prepared from control rats. In contrast, incubation of normal pituitary cells with serum from overfed rats for 3 days gave a significantly lower GH release than after incubation with serum from non-obese rats. In conclusion, cafeteria-dietinduced obese male Wistar rats have a decreased pituitary GH gene expression and a modifiable GH release in in vitro experiments. A possible role for peripheral circulating factors, like leptin and IGF-I, in decreasing the pituitary GH synthesis and release in obese rats is discussed.

Section: Discussioncontrasting

confidence: 59%

Section: Introductionmentioning

confidence: 99%

Pituitary growth hormone release and gene expression in cafeteria-diet-induced obese rats

Zhou¹,

Schepper²,

Craemer³

et al. 1998

“…Conversely, GH deficiency is associated with increased adiposity, reduced bone mass, and reduced lean muscle mass (de Boer et al 1995). Both dietary-and age-associated increases in adiposity are associated with a reduction in spontaneous (Veldhuis et al 1991, Vahl et al 1997 and stimulated (Williams et al 1984, Renier et al 1990, Cordido et al 1995, 2010, Makimura et al 2008 GH secretion. This results in an overall reduction in circulating levels of GH.…”

Section: Introductionmentioning

confidence: 99%

Increased adiposity and insulin correlates with the progressive suppression of pulsatile GH secretion during weight gain

Steyn

Xie

Huang

et al. 2013

Pathological changes associated with obesity are thought to contribute to GH deficiency. However, recent observations suggest that impaired GH secretion relative to excess calorie consumption contributes to progressive weight gain and thus may contribute to the development of obesity. To clarify this association between adiposity and GH secretion, we investigated the relationship between pulsatile GH secretion and body weight; epididymal fat mass; and circulating levels of leptin, insulin, non-esterified free fatty acids (NEFAs), and glucose. Data were obtained from male mice maintained on a standard or high-fat diet. We confirm the suppression of pulsatile GH secretion following dietary-induced weight gain. Correlation analyses reveal an inverse relationship between measures of pulsatile GH secretion, body weight, and epididymal fat mass. Moreover, we demonstrate an inverse relationship between measures of pulsatile GH secretion and circulating levels of leptin and insulin. The secretion of GH did not change relative to circulating levels of NEFAs or glucose. We conclude that impaired pulsatile GH secretion in the mouse occurs alongside progressive weight gain and thus precedes the development of obesity. Moreover, data illustrate key interactions between GH secretion and circulating levels of insulin and reflect the potential physiological role of GH in modulation of insulin-induced lipogenesis throughout positive energy balance. Key Words" pulsatile GH secretion " dietary-induced weight gain " insulin " non-esterified free fatty acids " adiposity

“…Conversely, plasma GH levels are reduced in food-restricted or fasted rodents (Tannenbaum et al 1979). In the obese state, both basal and stimulated secretion of GH is reduced in man (Williams et al 1984) and rodents (Renier et al 1990).…”

Section: Introductionmentioning

confidence: 99%

Chronic food-restriction alters the expression of somatostatin and growth hormone-releasing hormone in the ovariectomised ewe

Henry¹,

Rao²,

Tilbrook³

et al. 2001

Changes in the secretion of GH induced by long-term alterations in nutritional status are thought to result from alterations in somatostatin (SRIF) and growth hormonereleasing hormone (GHRH) at the level of the hypothalamus. To date however, the effect of nutrition on the gene expression of SRIF and GHRH in a species where GH secretion is increased by food restriction, as is the case for the sheep and human, remains unknown. We determined the effect of under-nutrition on the expression of SRIF and GHRH in the hypothalamus of sheep. Ovariectomised ewes were randomly divided into two groups and either fed an ad lib diet (n=6) or a restricted diet of 500 g lucerne chaff per day (food-restricted; n=5) for 7 months. In situ hybridisation was used to study hypothalamic gene expression for GHRH, SRIF and galanin (GAL). The food-restricted animals had elevated plasma concentrations of GH; this was associated with an increase in GHRH mRNA levels in the arcuate nucleus (ARC) and reduced SRIF in the rostral periventricular nucleus and ventromedial hypothalamic nucleus. The level of gene expression of GAL in the ARC and SRIF in the caudal periventricular nucleus was similar in ad lib and food-restricted animals. In conclusion, the effect of chronic food-restriction on the secretion of GH reflects increased GHRH and reduced SRIF synthesis in the hypothalamus.