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- Title
The Hypothalamic Sensing of Amino Adds Regulates Plasma Triglycerides.
- Authors
Gutierrez-Juarez, Roger; Band, Victor; Lam, Tony K.; Pocal, Allesandro; Rossetti, Luciano
- Abstract
Hypothalamic centers monitor the availability of circulating nutrients via nutrient-dependent peripheral signals (e.g., leptin and insulin) as well as via direct metabolic signals. The activation of these central nutrient sensors curtails food intake and endogenous glucose production (GP) and VLDL-Triglyceride secretion (VLDL-TG). Recently, we reported a novel biochemical pathway by which the mediobasal hypothalamus couples amino acid sensing to liver glucose output to restrain GP. Here we examined whether amino acids play a role in the hypothalamic regulation of VLDL-TG production and secretion. During pancreatic-basal insulin clamp studies in rots the administration of leucine and other amino acids within the mediobasal hypothalamus (MBH) was sufficient to markedly suppress the levels of plasma and liver triglycerides (TG). This effect was reproduced by an equimolar MBH infusion of leucine's deaminated product α-keto-isocaproic acid (KIC). Metabolism of leucine to KIC is required for leucine's effect on plasma TGs, since inhibiting MBH activity of leucine transaminase (LT) during MBH leucine infusions prevented the effect. Since the activation of hypothalamic K-ATP channels is required for the central effects of glucose and KIC on plasma TGs, we also examined their role in the KIC-mediated effects. The co-infusion of K-ATP channel blockers negated the effects of MBH KIC on plasma TGs. To further understand the hypotriglyceridemic effect of amino acids we next determined the hepatic levels of TGs in the same animals. The results showed that liver TGs changed in parallel with plasma TGs under the various conditions tested. Of interest, central leucine very potently decreased liver TG levels. Furthermore, preliminary studies showed that MBH leucine administration decreases the rate of VLDL-TG secretion as measured after tyloxapol administration. Thus, here we report a novel potential role of central amino acids sensing in the regulation of triglyceride metabolism.
- Publication
Diabetes, 2007, Vol 56, pA97
- ISSN
0012-1797
- Publication type
Academic Journal