Invited ReviewThe rise, fall, and resurrection of the ventromedial hypothalamus in the regulation of feeding behavior and body weight
Introduction
For researchers investigating satiety mechanisms in feeding behavior and body weight regulation, the ventromedial hypothalamus (VMH) was once the center of the universe. Between 1940 and 1980, there were hundreds of published studies of the effects of VMH lesions and stimulation or of knife cuts in and around the VMH. Then, almost as fast as you can say paraventricular hypothalamic nucleus (PVN), the VMH disappeared from many feeding researchers' vocabulary. Today, the VMH is not even included in some leading anatomists' schema of hypothalamic nuclei involved in feeding behavior [101], [312] and is barely mentioned in some reviews of the central (brain) control of feeding behavior (e.g., [352], [415]). Some biopsychology textbooks dismiss a role for the VMH entirely (e.g., [61], [315]). This paper reviews (in chronological order) the rise and fall of the VMH in feeding research, and after addressing the major issues that led to its demise, concludes that dismissal of a role for the VMH in feeding behavior and body weight regulation was premature.
Some researchers use the term ventromedial hypothalamus to refer either to a general area (e.g., [80], [117]) or to the ventromedial hypothalamic nucleus and arcuate nucleus (ARC) combined (e.g., [240]). In this paper, VMH refers only to the VMH nucleus, its capsule (shell), and dendritic branches. When the ARC was purposely included in a study, or the target (of lesions or stimulation) was not the VMH nucleus itself but instead was the basomedial hypothalamus (i.e., the ventral and medial portion of the hypothalamus, hereafter referred to as the VMH area), that will be specifically indicated. The abbreviation “VMH” (rather than VMN) follows the nomenclature of the widely used stereotaxic atlas by Paxinos and Watson [310].
Section snippets
Fröhlich's syndrome and early experimental studies
An obesity syndrome in humans that was associated with abnormalities of the basomedial hypothalamus was reported as early as 1840 [277]. This was initially attributed to endocrine imbalances due to dysfunction of the pituitary gland [17], [124] and eventually came to be known as Fröhlich's syndrome. The belief that the obesity was due to pituitary dysfunction remained the prevailing view through the mid-1930s (e.g., [25], [82], [104], [195]).
The first challenge to the idea that Fröhlich's
The fall
Concerns regarding the role of the VMH in feeding behavior had been raised as early as the 1940s (see following discussion). Nevertheless, by 1970, the evidence in favor of the VMH as the brain's satiety center seemed so convincing that only a few researchers had challenged it. The fall was rapid. Enough contradictory evidence was obtained in the early 1970s that Richard Gold published a paper in 1974 with the title “Hypothalamic obesity: the myth of the ventromedial nucleus” [134]. An
Metabolic/autonomic disorders
In the late 1960s and afterwards, several groups reported a sex difference with electrolytic or goldthioglucose VMH lesions—female rats and mice gained substantially more weight than males [81], [189], [212], [345], [370], [372], even when gonadectomized first [189] or matched for age and preoperative weight [81]. A similar sex difference has been found for septal lesions [372], [410], posterodorsal amygdaloid lesions [221], stria terminalis transections [334], and intraventricular PCPA
Conclusions
Advances in science depend on replicable results, and to date no study has supported Gold's claim [134] that maximum weight gains following lesions in the basomedial hypothalamus are produced by lesions anterior to the VMH (see [6], [138], [161], [163], [165] for contradictory results). Gold also claimed that lesions restricted to the VMH do not cause overeating or weight gain and that the hyperphagia and weight gain was due instead to damage to the VNAB or PVN. However, several groups reported
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