Plasticity of Brain α‐Adrenoceptors During the Development of Diet‐Induced Obesity in the Rat

Abstract

Male Sprague-Dawley rats, which are prone to develop diet-induced obesity (DIO) on a high energy (HE) diet can be separated from rats which are diet-resistant (DR) by several prospective tests. Using such tests, chow-fed DRl-prone rats have higher binding of 3H paraminoclonidine (PAC) to brain alpha2-adrenoceptors than do DIO-prone rats. These differences disappear after 3 months on a HE diet. To study the predictive value of these tests and possible associated changes in presynaptic membrane composition, brain alpha3(1-) (1nM 3H prazosin) and (alpha2-adrenoceptor (1nM) 3-H PAC) binding and synaptosomal fatty acid composition were assessed in 3-month-old male rats separated by weight gain into DR and DIO groups after 1 month on a HE diet. DIO had comparable total caloric intake but gained 30% and 43% more weight and were hyperinsulinemic compared to DR and chow-fed rats, respectively. After 1 month on a HE diet, DR rats still had 15%-53% higher 3H PAC binding than DIO and/or chow-fed rats in 14 of 16 brain areas assessed. A phenotype effect was present primarily in the amygdala where DR rats had higher 3H PAC binding than DIO rats. A diet effect was seen in some hypothalamic nuclei where both DR and DIO rats had higher 3H PAC binding than chow-fed rats. Conversely, DIO rats had 14%-21% higher 3H prazosin binding than DR rats in 3 brain areas. Changes in brain synaptosomal membranes' fatty acids reflected both phenotype and diet effects. Thus, while diet composition affects presynaptic membrane composition and alpha2-adrenoceptor binding in both DR and DIO rats, the predominance of plasticity of these parameters is limited to the brains of DR rats. This suggests that such plasticity may be an important determinant of the ability to resist the development of diet-induced obesity on a HE diet.

Metabolic imprinting: critical impact of the perinatal environment on the regulation of energy homeostasis

“…Rats which express the DIO phenotype have a number of inborn abnormalities of oxidative metabolism (Chang et al 1990), leptin (Levin & DunnMeynell 2002a-c;Levin et al 2003a,b) and insulin sensitivity (Clegg et al 2005), glucose sensing (Levin & Sullivan 1989;Levin et al 1996;Dunn-Meynell et al 2002;Tkacs & Levin 2004) and neuropeptide (Levin & Dunn-Meynell 1997;Levin 1999) and neurotransmitter function (Wilmot et al 1988;Levin 1990aLevin ,b, 1995Levin , 1996Hassanain & Levin 2002) which predispose them to become obese when fed a high-fat diet. In many cases, the development of obesity on such diets in adult rats is not associated with abnormal neural functions suggesting that obesity might be the 'normal' physiologic state of these animals (Wilmot et al 1988;Levin 1990aLevin ,b, 1994Levin & Hamm 1994;Levin et al 1996;Hassanain & Levin 2002;Levin & Dunn-Meynell 2002a-c). Whereas these pathways can be altered in adults, the developmental period is even more prone to diet-induced alterations in neural function.…”

The role of relaxin-3 and its receptor RXFP3 in defense of elevated body weight in diet-induced obesity

“…In addition to increased food intake, feed efficiency (the ratio of weight gained to calories consumed) was significantly increased in DIO rats compared to DR rats [76,77] . Because of the increased food intake and feed efficiency, only the HE-diet-fed DIO rats but not the HE-diet-fed DR rats developed visceral obesity, hyperleptinemia, hyperinsulinemia, hypercortisolemia, and dyslipidemia [20] .…”

Location and Effect of Obesity on Putative Anorectic Binding Sites in the Rat Brain

“…This diet contains 4.47 kcal/g, with 21% of the calories as protein, 3 1% as fat, and 48% as carbohydrate, 50% of which is sucrose (26). Rats were maintained on their respective diets for three months, at which time the eight highest and eight lowest weight gainers on the HE diet were classified as DIO and DR, respectively (19,25,(27)(28)(29)31). All rats were sacrificed by decapitation, without anesthetization, between 0800 and 1200 hours with food and water available ad libitum.…”

“…To avoid some of the problems associated with established obesity and the hyperglycemia which may also be present, we have used a model of dietinduced obesity (DIO) in the rat to study these anorectic binding sites (23). When male Sprague-Dawley rats were fed a diet moderately high in energy, fat and sucrose content (HE diet), about half developed DIO associated with hyperinsulinemia whereas the rest were DR, gaining the same amount of weight and carcass fat as chow-fed controls (19,25,(27)(28)(29)31). Although the excess weight gain of DIO rats was not necessarily caused by increased energy consumption, it was clear that these animals did not downregulate their caloric intake sufficiently to prevent the onset of DIO (25).…”

“…When male Sprague-Dawley rats were fed a diet moderately high in energy, fat and sucrose content (HE diet), about half developed DIO associated with hyperinsulinemia whereas the rest were DR, gaining the same amount of weight and carcass fat as chow-fed controls (19,25,(27)(28)(29)31). Although the excess weight gain of DIO rats was not necessarily caused by increased energy consumption, it was clear that these animals did not downregulate their caloric intake sufficiently to prevent the onset of DIO (25). One advantage of this model was that rats with a predisposition to develop DIO or DR phenotypes could be identified before HE diet exposure to assess factors which promoted the development of obesity (20,28).…”