Amygdaloid lesion-induced obesity: relation to sexual behavior, olfaction, and the ventromedial hypothalamus

Abstract

Lesions of the amygdala have long been known to produce hyperphagia and obesity in cats, dogs, and monkeys, but only recently have studies with rats determined that the effective site is the posterodorsal amygdala (PDA)-the posterodorsal medial amygdaloid nucleus and the intra-amygdaloid bed nucleus of the stria terminalis. There is a sex difference; female rats with PDA lesions display greater weight gain than male rats. In the brains of female rats with obesity-inducing PDA lesions, there is a dense pattern of axonal degeneration in the capsule of the ventromedial hypothalamus (VMH) and other targets of the stria terminalis. Transections of the dorsal component of the stria terminalis also result in hyperphagia and obesity in female rats. Similar to rats with VMH lesions, rats with PDA lesions are hyperinsulinemic during food restriction and greatly prefer high-carbohydrate diets. The PDA is also a critical site for some aspects of rodent sexual behavior, particularly those that depend on olfaction, and the pattern of degeneration observed after obesity-inducing PDA lesions is remarkably parallel to the circuit that has been proposed to mediate sexual behavior. Medial amygdaloid lesions disrupt the normal feeding pattern and result in impaired responses to caloric challenges, and there is evidence that these behavioral changes are also due to a disruption of olfactory input. With its input from the olfactory bulbs and connections to the VMH, the PDA may be a nodal point at which olfactory and neuroendocrine stimuli are integrated to affect feeding behavior.

Intrahypothalamic pituitary adenylate cyclase-activating polypeptide regulates energy balance via site-specific actions on feeding and metabolism

“…Both brain regions have been strongly implicated in energy balance, so the MeA and LPB may be two distinct central pathways that converge on the PVN and VMN to manage both feeding behavior and metabolic systems. Lesions to the MeA produce hyperphagia and obesity, especially in females (31). Moreover, the MeA is also a glucose-sensing area of the brain that may respond to states of hypoglycemia, further strengthening a connection with the wellcharacterized glucostatic role of the VMN (62).…”

Estrogen replacement therapy induces functional asymmetry on an odor memory/discrimination test

“…In male rats, 17β-estradiol, but not the nonaromatizable androgen 5α-dihydrotesterone, significantly reverses the volume decrement of the left, but not right, posterodorsal nucleus of the medial amygdala (MePD) induced by castration (Cooke et al, 2003). The MePD has a high density of both ERα & ERβ receptors and plays a key role in integrating olfactory and neuroendocrine information (King, 2006). However, the mechanisms responsible for these effects are unlikely due to a simple left:right difference in estrogen receptor distribution, since the relative amount of ER mRNA-expression appears not to differ on the two sides of the brain (Shughrue and Merchenthaler, 2001).…”

MC4R-expressing glutamatergic neurons in the paraventricular hypothalamus regulate feeding and are synaptically connected to the parabrachial nucleus

“…We also injected AAV-Cre into the medial amygdala because, like the PVH, it has neurons that are SIM1 + , glutamatergic, and Mc4r-expressing (2, 10, 11, 27). Of relevance, the medial amygdala is heavily connected to the hypothalamus, has previously been associated with obesity (30,31), and MC4Rs in this site have been proposed to affect feeding (22). Finally, we also tested two SIM1 − sites, the nucleus of the solitary tract (NTS) and the lateral parabrachial nucleus (L-PBN), because they have glutamatergic and Mc4r-expressing neurons, and importantly, injections of MC3/4 receptor agonists into these sites affect energy balance (10,11,23,27).…”