Obesity Hypertension Is Related More to Insulin’s Fatty Acid Than Glucose Action

Author:

Egan Brent M.1,Hennes Magda M.I.1,Stepniakowski Konrad T.1,O’Shaughnessy Irene M.1,Kissebah Ahmed H.1,Goodfriend Theodore L.1

Affiliation:

1. From the Division of Clinical Pharmacology, Departments of Pharmacology and Medicine, Medical University of South Carolina, Charleston (B.M.E., K.T.S.); the Division of Endocrinology, Metabolism, and Clinical Nutrition, Department of Medicine, Medical College of Wisconsin, Milwaukee (M.M.I.H., I.M.O., A.H.K.); and the Departments of Medicine and Pharmacology, University of Wisconsin and William S. Middleton Veterans Memorial Hospital, Madison (T.L.G.).

Abstract

Abstract Although resistance to insulin-mediated glucose disposal has emerged as a link between abdominal obesity and hypertension, abnormalities of nonesterified fatty acid metabolism may play a greater role. Analyses were performed on existing data from 17 abdominally obese subjects (11 hypertensive, 6 normotensive) to determine whether fatty acid concentration and turnover were related to blood pressure independently of hyperinsulinemia and resistance to insulin-mediated glucose disposal. Glucose utilization, fatty acid concentration, and fatty acid turnover were obtained fasting and during euglycemic hyperinsulinemia at 10 and 40 mU·m −2 ·min −1 . Analyses were also performed on another group of 30 subjects with a wide range of risk factors who had blood pressure data as well as glucose and fatty acid measurements during an insulin tolerance test. Fatty acid concentration and turnover were markedly more resistant to suppression by insulin in obese hypertensive than in lean or obese normotensive individuals. In the 17 obese subjects, blood pressure measured at screening, in the laboratory, and over a period of 24 hours correlated significantly with fatty acid concentration and turnover but not with glucose disposal measured during the hyperinsulinemic clamp. These correlations remained significant after fasting insulin, the insulin area under the curve during an oral glucose tolerance test, and glucose disposal during the clamp were controlled for. In the second group of subjects, plasma fatty acids 15 minutes after intravenous insulin also correlated with blood pressure. These correlations remained significant after insulin and an index of sensitivity to insulin-mediated glucose disposal were statistically controlled for. The data indicate that blood pressure is related to the effects of insulin on fatty acid metabolism. The findings raise the possibility that resistance of hormone-sensitive lipase to insulin participates in elevating the blood pressure of abdominally obese hypertensive subjects by increasing fatty acid concentration and turnover.

Publisher

Ovid Technologies (Wolters Kluwer Health)

Subject

Internal Medicine

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