Central Leptin Stimulates Corticosterone Secretion at the Onset of the Dark Phase

Abstract

Leptin, a hormone secreted by adipose tissue in proportion to body adiposity, is proposed to be involved in the central nervous regulation of food intake and body weight. In addition, evidence is emerging that leptin regulates neuroendocrine and metabolic functions as well, presumably via its action in the central nervous system (CNS). To investigate this regulatory effect of leptin, we infused 3.5 ug of human leptin directly into the third cerebral ventricle (i3vt) of lean male Long-Evans rats, 90 min before the onset of their dark phase. Before and after infusion, blood samples were withdrawn through indwelling catheters for assessment of hormonal (plasma corticosterone, insulin, leptin), autonomic (plasma norepinephrine, epinephrine), and metabolic (plasma glucose) parameters. 13vt leptin caused an increase in plasma corticosterone and plasma leptin levels relative to the control condition. The effects of i3vt leptin on corticosterone secretion became particularly apparent after the onset of the dark phase. The results of the present study indicate that i3vt leptin stimulates the hypothalamo-pituitary-adrenal (HPA) axis, particularly when rats normally encounter their largest meals. These results are consistent with the possibility that high circulating leptin levels may underlie the increased activity of the HPA axis that is generally characteristic of human obesity and most animal models of obesity. Diabetes 46:1911-1914, 1997 L eptin (OB protein), the protein encoded by the obese gene, has rapidly emerged as a key substance in the regulation of metabolism, adiposity, and food intake (1). It is secreted from white adipose tissue in direct proportion to the amount of stored triglycerides (2), and it interacts with specific receptors in hypothalamic areas important in the control of food intake and metabolism (3). Because its local administration into the brain results in reduced food intake (4-6), increased energy expenditure (7), and, if prolonged over days, decreased adiposity (8), leptin has been suggested to be an important negative feedback signal in the control of these parameters (9).Consistent with this view, many species including primates and rodents secrete less leptin when they have been deprived of food (10) and have an increase in circulating leptin during states of positive energy balance (11). Because peripheral administration of leptin to fasting mice reverses fastinginduced changes of the adrenal, thyroid, and gonadal axes (12,13), it is reasonable to hypothesize that changes of leptin levels related to the nutritional state may normally regulate neuroendocrine activity. Related to this, leptin may modulate autonomic outflow, since leptin administration in ob/ob mice stimulates norepinephrine turnover in brown adipose tissue (BAT) (14).There is a diurnal pattern of leptin secretion, with plasma leptin levels roughly correlating with diurnal patterns of food intake. This rhythm has been proposed to modulate circadian rhythmicity of the hypothalamo-pituitary-adrenal (HPA) axis (12). To invest...

Leptin Downregulates LPS-Induced Lung Injury: Role of Corticosterone and Insulin

“…Nevertheless, studies examining the effects of leptin on the corticosterone levels have been controversial. Central administration of leptin has been shown to increase plasma corticosterone levels in rats [44], and systemic administration of leptin also increased corticosterone levels 60 and 120 min postinjection [45]. However, leptin was found to decrease the preparturient increase in adrenocorticotropic hormone and cortisol in the sheep fetus [46]; additionally, in diabetes, in which there is a well-documented decrease in leptin levels, there is a concurrent increase in HPA activity [47].…”

Chronic central leptin infusion modulates the glycemia response to insulin administration in male rats through regulation of hepatic glucose metabolism

“…The increase in leptin expression could be related to an increase in insulin sensitivity, as this hormone augments leptin synthesis in fat (Saladin et al, 1995; Different symbols refer to significant differences between groups, "*" different from C, "#" from CI, "&" from PF, "o" from PFI and "$" from L. Significance: p < 0.05 in panels C, F and G; p < 0.01 in panels E and H and p < 0.001 in panel D. Wabitsch et al, 1996) and its deficiency down-regulates leptin mRNA in adipose tissue (MacDougald et al, 1995). Central leptin infusion has also been demonstrated to increase plasma corticosterone (Van Dijk et al, 1997) that augments leptin in adipose tissue (Fried et al, 2000).…”

Excess Catecholamine Syndrome: Pathophysiology and Therapya

“…16 As regards mechanisms linking overweight to increased sympathetic outflow of the brain, leptin may play a role. 17,18 Furthermore, glucose‐sensitive neurons of the hypothalamus could influence sympathetic outflow of the brain. 19 Favoring glucose‐linked signals is the finding that a glucose load raises sympathetic activity particularly in elderly persons.…”