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A Low-Protein Diet Blocks Development of Hyperphagia and Obesity in Rats with Hypothalamic Knife Cuts^1,2,3,4,

Human Nutrition Research Program, Cooperative Research, Lincoln University, Jefferson City, MO 65102-0029

The objective of this study was to examine the influence of dietary protein levels on development of hyperphagia and obesity in rats that had been given surgical knife cuts between the ventromedial and lateral areas of the hypothalamus. Under normal conditions, rats with this type of surgery exhibit hyperphagia and become obese when given unlimited access to dietary energy. Earlier studies indicated impaired adaptive diet-induced thermogenesis in response to excess energy intake in this animal model of obesity. Because low protein diets can also stimulate diet-induced thermogenesis, we conducted four experiments which examined how diets containing different levels of protein affect development of hyperphagia and obesity in female rats given bilateral, parasagittal wire knife cuts between the ventromedial and lateral areas of the hypothalamus. For 28 d, knife-cut and sham-operated rats were given unlimited or restricted (179 or 180 kJ/d) access to diets containing protein at 5, 10 or 20% of total metabolizable energy. Knife-cut rats with unlimited access to 10 or 20% protein diets became obese, gaining 2–3 times more weight and 3–6 times more carcass energy while consuming 55–89% more energy than sham-operated rats. In contrast, energy consumed and gained by knife-cut rats with unlimited access to a 5% protein diet was similar to that of rats given sham surgery. Results indicate that a low protein diet effectively blocks development of hyperphagia and obesity in rats with surgical knife cuts between the ventromedial and lateral regions of the hypothalamus.

KEY WORDS: • energy balance • obesity • ventromedial hypothalamus • protein • rats

¹ Presented in part at Annual Meetings of the Federation of American Societies for Experimental Biology, May 1–5, 1988, Las Vegas, NV and March 19–23, 1989, New Orleans, LA [Vander Tuig, J. G., Beneke, W. M. & Davis, C. H. (1988) A low protein diet inhibits development of obesity in rats with hypothalamic knife cuts. FASEB J. 2: A1221 (abs.) and Vander Tuig, J. G. & Beneke, W. M. (1989) Further evidence that hypothalamic obesity is prevented by a low protein diet. FASEB J. 3: A353 (abs.)].

² Supported by USDA CSRS Projects MO-X-OH85-511 and MO-X-OH91-519.

³ Lincoln University Cooperative Research manuscript number A5-101-95.

⁴ The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 USC section 1734 solely to indicate this fact.

⁵ To whom correspondence should be addressed.

Manuscript received 19 June 1995. Revision accepted 7 February 1996.