Contribution of growth, fatness, and activity to weight disturbance after septohypothalamic cuts in adult hamsters.

Abstract

The mechanism responsible for weight stability in adult hamsters was investigated by (a) transecting the dorsoventrally oriented nerve pathways between the septal area and hypothalamus (SH cuts) and (b) partitioning the observed increases in the rate of weight gain into three contributory components: changes in somatic growth, in body fatness, and in energy expended as voluntary activity on horizontal disks. Between 60% and 70% of the weight increase after SH cuts was due to acquisition of lean body mass, and 30%-40% of weight increase consisted of excess body fat. After SH cuts, serum growth hormone and insulin concentrations were increased on Day 14, food intake was increased between Day 2 and Day 42, skeletal lengths were greater on Day 77, and voluntary activity levels were 84% lower on Days 10-45, relative to control hamsters. It is concluded that dorsoventrally oriented nerve pathways in the septal area are involved in the control of growth, maintenance of body fat reserves, and voluntary activity and that they contribute to the maintenance of stable body weight in adult hamsters.Around the time of puberty rodent maintenance of stable weight has commonly weight attains a stable plateau (Monteiro & been labeled a regulation, although its Falconer, 1966; Slob & Van der Werff ten mechanism is not understood. Bosch, 1975;Widdowson & McCance, 1960).The prevailing view is that regulation of This weight level is defended against upward body fat reserves (Kennedy, 1957) accounts (Cohn & Joseph, 1962) or downward (Borer for weight stability in adult mammals and & Kooi, 1975; Levitsky, Faust, & Classman, that any shifts in weight plateau represent 1976) deflections imposed by changes in the shifts in body fat stores (Keesey & Powley, available nutrient energy. Such active 1975). The neural substrate for this weightand fat-regulatory mechanism was initially This research was supported in part by Grants localized in the medial basal area of hypo-RO3M29877 from the National Institute of Mental thalaniUS (MBH), because destruction of Health and PCM78-07626 from the National Science MBH led to increases in body weight, body Foundation to K. T. Borer We thank E S. Valenstein, f t ( Be rnardis & Frohman, 1971; Bernardis N. Radm, and B. Agranoff for the use of some equip-" 01 , -,n^r i-mr-i^ ir>/-«n TT ii_ • j. o ment and facilities, Mara Markovs and Sarah Browne & Skelton , 1965/1966 Hethermgton & for technical assistance, and Neil Rowland for com-RanSOn, 1940), and Serum insulin levels ments that helped improve the manuscript.

Hippocampal serotonin mediates hypoactivity in dietarily obese hamsters: A possible manifestation of aging?

“…In the hamster, voluntary running levels are reduced by 80% following electrocoagulative lesions of rostromedial septum (10), horizontal transection of septo-hippocampal interconnections (9), or bilateral transections of dorsal hippocampus (11), while at the same time these neurosurgical procedures induce striking acceleration of somatic growth and some accumulation of body fat. These observations suggest that septo-hippocampal neural circuits participate in the bioenergetic modulation of spontaneous running in hamsters in that they suppress somatic growth and accumulation of fat at the same time that they stimulate spontaneous running activity.…”

Counterregulation of insulin by leptin as key component of autonomic regulation of body weight

“…The inverse relationship between body fat and activity levels is associated with neurochemical changes in brain areas where damage produces obesity and hypoactivity [293] . Obesity-inducing brain lesions in hamsters abolish the inverse relationship to body fat [292] . This then indicates a neurochemical link between the nonhomeostatic physical activity and body fat and body mass.…”

“…Several lines of experimental animal research confirm the inverse relationship between spontaneous physical activity and body fatness. Obesity induced by either VMH lesions in rats [23] , rostromedial septal lesions [290] and hippocampal [291] or septo-hypothalamic transections [292] in hamsters, or cafeteria and high-fat diets in neurologically intact animals [3,293,294] reduce spontaneous running activity. On the other hand, severe dietary restriction consisting of only 2-h access to food, leads to weight loss in rats and up to 300% to 500% increase in spontaneous running activity to the point of emaciation [295] .…”

“…[317] , and changes in body fat level are accompanied by changes in lean mass. In the hamster, rostral septal lesions [290] and hippocampal [291] and septo-hypothalamic [292] transections increase obesity but also elicit bone and lean body mass growth and an upward displacement of regulated body mass setpoint. Remarkably, increases in body mass setpoint without obesity also can be triggered by voluntary running in this species [318] proving Gordon Kennedy right about the interconnectedness of voluntary activity, weight regulation, and body growth [30,[319][320][321] .…”

“…That this is a maturational event is seen by growth acceleration not being possible during animals' natural early rapid growth [323] . The requirement for growth cessation before the defenses of stable adult weight against downward deflections are initiated is shown by the necessity of pituitary gland presence for acceleration of growth by exercise [324] , increased pulsatile oversecretion of growth hormone during that growth [325,326] , and increased pulsatile growth hormone secretion after the disruption of the brain substrates involved in the maintenance of weight stability in nongrowing animals [290][291][292] . Finally, the permanence of neural changes involved in the defense of the growth-induced upward displacement of body mass setpoint is seen in the phenomenon of catch-up growth [325] .…”