Improved insulin sensitivity and metabolic flexibility in ghrelin receptor knockout mice.

Abstract

Stimulation of the ghrelin receptor (GhrR) by ghrelin results in a variety of metabolic changes including increased food intake, fat storage and insulin resistance. Loss of ghrelin signaling is protective against diet-induced obesity, suggesting that ghrelin plays a significant homeostatic role in conditions of metabolic stress. We examined glycemic control in GhrR -/- mice fed a high-fat diet, and used indirect calorimetry to assess fuel substrate usage and energy expenditure. GhrR -/- mice fed a high-fat diet had several measures of greater insulin sensitivity, including: lower fasted blood glucose and plasma insulin, lower %Hb(A1c), lower insulin levels during glucose tolerance tests, and improved performance in hyperinsulinemic-euglycemic and hyperglycemic clamp studies. GhrR -/- mice fed a high-fat diet did not develop hepatic steatosis and had lower total cholesterol, relative to controls. Furthermore, GhrR -/- mice demonstrated a lower intestinal triglyceride secretion rate of dietary lipid. GhrR -/- mice have higher respiratory quotients (RQ), indicating a preference for carbohydrate as fuel. The range of RQ values was wider in GhrR -/- mice, indicating greater metabolic flexibility and insulin sensitivity in these animals. We therefore propose that loss of ghrelin signaling promotes insulin sensitivity and metabolic flexibility, and protects against several fatty diet-induced features of metabolic syndrome due to convergent changes in the intake, absorption and utilization of energy.

• Authors: Kenneth A Longo, Soratree Charoenthongtrakul, Derek J Giuliana, Elizabeth K Govek, Thomas McDonagh, Yong Qi, Peter S DiStefano, Brad J Geddes
• Journal: Regulatory peptides (Regul Pept) Vol. 150 Issue 1-3 Pg. 55-61 (Oct 09 2008) ISSN: 0167-0115 [Print] Netherlands
• PMID: 18453014 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Blood Glucose
• Dietary Fats
• Glycated Hemoglobin A
• Insulin
• Receptors, Ghrelin
• Triglycerides
• Cholesterol

Topics

• Animals
• Blood Glucose (analysis)
• Calorimetry, Indirect (methods)
• Cholesterol (metabolism)
• Dietary Fats (administration & dosage, metabolism, pharmacology)
• Energy Metabolism (physiology)
• Fasting
• Glucose Tolerance Test
• Glycated Hemoglobin (analysis, metabolism)
• Insulin (blood)
• Insulin Resistance (physiology)
• Mice
• Mice, Knockout
• Receptors, Ghrelin (genetics)
• Triglycerides (metabolism)