Vagal Hyperactivity Due to Ventromedial Hypothalamic Lesions Increases Adiponectin Production and Release

Abstract

In obese humans and animals, adiponectin production and release in adipose tissue are downregulated by feedback inhibition, resulting in decreased serum adiponectin. We investigated adiponectin production and release in ventromedial hypothalamic (VMH)-lesioned animals. VMH-lesioned mice showed significant increases in food intake and body weight gain, with hyperinsulinemia and hyperleptinemia at 1 and 4 weeks after VMH-lesioning. Serum adiponectin was elevated in VMH-lesioned mice at 1 and 4 weeks, despite adipocyte hypertrophy in subcutaneous and visceral adipose tissues and increased body fat. Adiponectin production and mRNA were also increased in both adipose tissues in VMH-lesioned mice at 1 week. These results were replicated in VMH-lesioned rats at 1 week. Daily atropine administration for 5 days or subdiaphragmatic vagotomy completely reversed the body weight gain and eliminated the increased adiponectin production and release in these rats, with reversal to a normal serum adiponectin level. Parasympathetic nerve activation by carbachol infusion for 5 days in rats increased serum adiponectin, with increased adiponectin production in visceral and subcutaneous adipose tissues without changes of body weight. These results demonstrate that activation of the parasympathetic nerve by VMH lesions stimulates production of adiponectin in visceral and subcutaneous adipose tissues and adiponectin release, resulting in elevated serum adiponectin.

Olanzapine‐induced early cardiovascular effects are mediated by the biological clock and prevented by melatonin

“…Parasympathetic activity plays a key role in blood pressure regulation, adiposity and metabolic activity.Acutely, olanzapine induces a potent increase of parasympathetic tone translated into a decrease in blood pressure and heart rate in rats and postural hypotension in humans. Parasympathetic hyperactivation may contribute to the development of metabolic syndrome, obesity or other SGA‐induced adverse metabolic effects. Our anatomical analysis shows that olanzapine activates the parasympathetic branch of the ANS, with melatonin vastly mitigating this effect.…”

“…The biological clock selectively coordinates ANS balance to influence metabolism in different parts of the body, so alteration of this output may over time precipitate problems in metabolism such as the metabolic syndrome. Acute parasympathetic activation induces adiposity and an increase in plasmatic adiponectin. Such effects are also observed with short‐term treatment with olanzapine.…”

Non‐alcoholic fatty liver disease as a consequence of autonomic imbalance and circadian desynchronization

“…The circulating levels of high‐molecular‐weight adiponectin in healthy humans follow circadian variations that are not driven by the feeding–fasting cycle . This rhythm may be based upon the activity of the autonomic branches since in vitro and in vivo studies have shown that sympathetic/β‐adrenergic stimulation of adipose tissue inhibits the production and secretion of adiponectin , whereas parasympathetic activation increases it . Thus, it is possible that in the course of NAFLD, an enhanced sympathetic and/or decreased parasympathetic input to adipose tissue may result in decreased adiponectin levels, contributing to disease progression.…”

Subdiaphragmatic Vagotomy With Pyloroplasty Ameliorates the Obesity Caused by Genetic Deletion of the Melanocortin 4 Receptor in the Mouse

“…In the case of VMH lesions, a unique enhancement of parasympathetic vagal nerve activity is produced that is associated with increased insulin, gastric acid secretion, gastric emptying, and gastrointestinal cell proliferation (Hales and Kennedy, 1964 ; Ridley and Brooks, 1965 ; Frohman and Bernardis, 1968 ; Frohman et al, 1969 ; Han and Frohman, 1970 ; Bernardis and Frohman, 1971 ; Inoue et al, 1977 , 1983 ; Jeanrenaud, 1978 ; Berthoud and Jeanrenaud, 1979 ; Bray and York, 1979 ; Inoue and Bray, 1979 , 1980 ; Sawchenko, 1979 ; Weingarten and Powley, 1980 ; Bray et al, 1981 ; Cox and Powley, 1981a ; Bray, 1984 ; Yoshimatsu et al, 1984 ; Duggan and Booth, 1986 ; Kiba et al, 1992 , 1993 , 1996 ; Kintaka et al, 2009 ; Suzuki et al, 2014 ), which in the case of hyperinsulinemia and gastric hyperacidity is counteracted by SDV (Powley and Opsahl, 1974 ; Inoue and Bray, 1977 ; Berthoud and Jeanrenaud, 1979 ).…”