Angiotensin II reduces food intake by altering orexigenic neuropeptide expression in the mouse hypothalamus.

Abstract

Angiotensin II (Ang II), which is elevated in many chronic disease states such as end-stage renal disease and congestive heart failure, induces cachexia and skeletal muscle wasting by increasing muscle protein breakdown and reducing food intake. Neurohormonal mechanisms that mediate Ang II-induced appetite suppression are unknown. Consequently, we examined the effect of Ang II on expression of genes regulating appetite. Systemic Ang II (1 μg/kg · min) infusion in FVB mice rapidly reduced hypothalamic expression of neuropeptide Y (Npy) and orexin and decreased food intake at 6 h compared with sham-infused controls but did not change peripheral leptin, ghrelin, adiponectin, glucagon-like peptide, peptide YY, or cholecystokinin levels. These effects were completely blocked by the Ang II type I receptor antagonist candesartan or deletion of Ang II type 1a receptor. Ang II markedly reduced phosphorylation of AMP-activated protein kinase (AMPK), an enzyme that is known to regulate Npy expression. Intracerebroventricular Ang II infusion (50 ng/kg · min) caused a reduction of food intake, and Ang II dose dependently reduced Npy and orexin expression in the hypothalamus cultured ex vivo. The reduction of Npy and orexin in hypothalamic cultures was completely prevented by candesartan or the AMPK activator 5-aminoimidazole-4-carboxamide ribonucleoside. Thus, Ang II type 1a receptor-dependent Ang II signaling reduces food intake by suppressing the hypothalamic expression of Npy and orexin, likely via AMPK dephosphorylation. These findings have major implications for understanding mechanisms of cachexia in chronic disease states such as congestive heart failure and end-stage renal disease, in which the renin-angiotensin system is activated.

• Authors: Tadashi Yoshida, Laura Semprun-Prieto, Richard D Wainford, Sergiy Sukhanov, Daniel R Kapusta, Patrice Delafontaine
• Journal: Endocrinology (Endocrinology) Vol. 153 Issue 3 Pg. 1411-20 (Mar 2012) ISSN: 1945-7170 [Electronic] United States
• PMID: 22234465 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Intracellular Signaling Peptides and Proteins
• Neuropeptide Y
• Neuropeptides
• Orexins
• Angiotensin II
• Cholecystokinin

Topics

• Angiotensin II (metabolism)
• Animals
• Cachexia (metabolism)
• Cholecystokinin (metabolism)
• Eating (drug effects)
• Feeding Behavior
• Gene Expression Regulation
• Hypothalamus (metabolism)
• Infusions, Intraventricular
• Intracellular Signaling Peptides and Proteins (metabolism)
• Mice
• Mice, Inbred C57BL
• Mice, Transgenic
• Neuropeptide Y (metabolism)
• Neuropeptides (biosynthesis, chemistry, metabolism)
• Orexins
• Phosphorylation
• Time Factors