High-fat diets induce a rapid loss of the insulin anorectic response in the amygdala

Abstract

(FI). The central bed nucleus of the amygdala (CeA), as other regions of the brain regulating feeding behavior, expresses insulin receptors. Our objectives were to show an insulin anorectic response in the amygdala, study the effect of high-fat diets on this response, and map the neural network activated by CeA insulin using c-Fos immunohistochemistry. Sprague-Dawley (SD) rats fitted with unilateral CeA cannulas were adapted to a low-fat (LFD) diet before they were fed a high-fat diet (HFD). Their feeding response to CeA saline or insulin (8 mU) was tested after 24 h, 72 h, or 7 days of being on a HFD. In a second experiment, SD rats were fed the HFD for 3, 7, or 49 days and were then refed with the LFD. They were tested for their insulin response before and after an HFD and every 3 days for the following weeks. Insulin tolerance tests were performed in a parallel group of rats. The CeA insulin stimulation c-Fos expression was studied to identify the distribution of activated neuronal populations. Feeding an HFD for 72 h or more induced a CeA, but not peripheral, insulin resistance, which was slowly reversed by LFD refeeding. The duration of HFD feeding determined the time frame for reversal of the insulin resistance. CeA insulin increased c-Fos in multiple brain regions, including the arcuate nucleus/paraventricular nucleus region of the hypothalamus. We conclude that the amygdala may be an important site for insulin regulation of food intake and may have a significant role in determining susceptibility to HFD-induced obesity. rat; food intake; central insulin sensitivity; limbic system THE INCREASING INCIDENCE OF obesity and type 2 diabetes presents a major health challenge, as well as a huge economic burden upon health care systems. Understanding the etiology of this "diabesity pandemic" (45), insulin resistance (23), and associated pathologies of the metabolic syndrome is essential if this epidemic is to be reversed. Environmental factors, such as the lack of exercise or the excessive consumption of food, associated with modern life styles, have been linked to the development of insulin resistance.Food intake regulation and energy balance are achieved through a complex coordination of peripheral signals and central regulatory circuitry (8,25). These processes determine the initiation, termination, size, composition and frequency of meals, and the long-term regulation of food intake in relation to body energy requirements. The hypothalamus has a central role in the regulation of feeding and of energy expenditure (52). It receives a variety of endocrine, neural, or metabolic information, relating the current status of body energy stores and feeding activity and integrates this information to help regulate the efferent pathways and match energy intake to energy expenditure. Central to these control mechanisms are the arcuate nuclei, the paraventricular nucleus (PVN), and the lateral hypothalamus, which are particularly important for the control of food intake (8, 25, 32, 52). However, many other regions of the...

High cerebral insulin sensitivity is associated with loss of body fat during lifestyle intervention

“…At that time, we speculated that fatty acids derived from visceral fat depots may cause insulin resistance of the brain and therefore lead to further weight gain. Indeed, recent studies confirmed that intracerebroventricular palmitic acid infusion and high-fat diet induce insulin resistance in different brain regions in mice and rats [12,14,15]. These observations, together with the present finding of high insulin sensitivity in the brain associated with lower intake of saturated fat, may suggest that insulin resistance in the brain elevates serum concentrations of saturated fatty acids not only by increasing visceral fat mass, but also more directly by decreasing physical activity and increasing intake of saturated fat.…”

Pituitary Adenylate Cyclase-Activating Peptide in the Central Amygdala Causes Anorexia and Body Weight Loss via the Melanocortin and the TrkB Systems

“…The CeA, indeed, plays a key role in the non-homeostatic regulation of feeding and the regulation of macronutrient selection (King et al, 1998;Will et al, 2004). Rats with ablation of the CeA display a reduction in body weight as well as lower preferences for tasty solutions (Touzani et al, 1997), and the activation/inhibition of specific neuropeptide/hormone receptors or cell types within the CeA has been shown to modulate food intake, especially if palatable (Boghossian et al, 2009;Primeaux et al, 2006). The CeA has also recently been implicated in excessive eating .…”

Insulin Signals Through the Dorsal Vagal Complex to Regulate Energy Balance

“…In fact, insulin receptor knockdown in the catecholaminergic neurons of the ventral tegmental area increases body weight and fat mass in mice (14), whereas direct injection of insulin into the central bed nucleus of the amygdala decreases food intake in healthy but not high fat-fed rodents (15). Insulin responsiveness in the dorsal vagal complex (DVC) and the subsequent control on glucose homeostasis have also been examined (16).…”