Macronutrient Intake, Growth Hormone-Releasing Factor and Somatostatin During Zinc Deficiency and Repletion in Rats

133 p.Thesis (Ph.D.)--University of Illinois at Urbana-Champaign, 1998.The biochemical mechanisms contributing to 'zinc deficiency-induced anorexia' are not understood, although the recent discovery of hypothalamic appetite-controlling neuropeptides suggests that this anorexia may ultimately be explained within the brain. In a series of experiments, we have characterized the macronutrient feeding patterns of zinc-deficient (Zn$-$) and zinc repleted rats in an effort to identify potential neural factors involved in zinc deficiency-induced anorexia and subsequent repletion. Sprague-Dawley outbred rats were provided three food dishes simultaneously each containing mixtures of carbohydrate (CHO), protein (PRO) or fat (FAT) made either adequate (Zn+) or deficient in zinc. After 28 days of free access to the diets, the Zn$-$ animals were allowed access to the Zn+ diets, termed 'zinc repletion'. Our results indicated that the reduction in total food intake observed in Zn$-$ rats was the result of decreased CHO intake, and approximately 25% of the Zn$-$ rats switched their dominant macronutrient preference ($>$50% total kcal) from CHO to FAT. There were no alterations in the normal diurnal macronutrient pattern of intake in Zn$-$ rats regardless of macronutrient intake changes. We did not note any change in protein intake in Zn$-$ rats, but during zinc repletion, PRO intake increased for 1-3 days. Growth hormone-releasing factor (GRF) has been shown to stimulate the preference for PRO intake. Total peptide content, in vitro release, and mRNA levels of GRF and it's counter-regulatory partner, somatostatin (SRIF), were measured in Zn$-$ and zinc repleted rats to determine if these peptides correlated with the transient increase in protein intake observed in zinc repletion. There were no differences in total GRF content or GRF mRNA in Zn$-$ or zinc repleted rats, but in vitro GRF release increased 3-fold during repletion. Basal SRIF secretion decreased, while SRIF mRNA levels increased during zinc repletion compared to Zn$-$ rats. Using immunoneutralization to block endogenous levels of GRF, we observed decreased protein intake and increased carbohydrate and fat intake in Zn$-$ animals receiving i.c.v. infusion of anti-GRF IgG compared to vehicle controls. In summary, GRF may direct protein intake, and possibly CHO and FAT intake, during zinc repletion to supply anabolic substrates for growth.U of I OnlyRestricted to the U of I community idenfinitely during batch ingest of legacy ETD