Hypothalamic Lesions Induce Obesity and Sex-Dependent Glomerular Damage and Increases in Blood Pressure in Rats

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Abstract
Abstract Placement of two symmetrical lesions in the ventromedial hypothalamus of the rat causes massive overeating and obesity. We have studied male (n=8) and female (n=5) Munich-Wistar rats 7 months after induction of obesity and compared them with age-matched controls. Body weight and kidney weight were greater in control males versus females (396±7 and 1.5±0.1 g versus 229±4 and 1.0±0.1 g, respectively; both P <.001). Both obese males and females were heavier than lean counterparts (592±30 and 361±19 g, both P <.001), whereas kidney weight was similar between obese and control rats of each sex (obese males, 1.5±0.1 g; obese females, 1.1±0.1 g). Blood pressure was higher in obese versus control males; there were no differences between other groups. Single-nephron glomerular filtration rate was similar in control females and males and obese females but depressed in obese males. Glomerular blood pressure was normal in all groups. Urinary protein excretion and the percentage of sclerosed glomeruli were similar in control females and males and obese females but elevated in obese males. Plasma triglyceride levels were elevated in obesity, particularly in males. We conclude that hypothalamic lesioning induces overeating and obesity and selectively in the male causes hypertension and glomerular damage as well as declines in renal function. This injury is not hemodynamically mediated (glomerular blood pressure is normal) but may be related to the elevation in plasma triglyceride levels, which has previously been causally linked to glomerular damage in genetically obese rats.