High serum oxytocin is associated with metabolic syndrome in older men – The MINOS study
Introduction
Oxytocin (OT) is a nonapeptide synthesized by supraoptic and paraventricular hypothalamic nuclei and secreted by the posterior lobe of the pituitary gland. It stimulates milk ejection and uterine contractility, regulates responses to stressors and modulates social interactions [1].
OT regulates caloric intake and body weight. Exogenous OT reduces caloric intake in humans [2]. In monkeys, chronic OT administration inhibits food intake and produces weight loss [3]. OT deficient mice and OT receptor-deficient mice develop obesity [4]. By contrast, data on the serum OT levels in obese individuals and those concerning the effect of food intake on serum OT levels are discordant [5], [6].
OT regulates the metabolism of carbohydrates and lipids. In healthy men OT administered intravenously increased serum levels of glucagon and glucose which was followed by an increase in insulin concentration [7]. This effect may be mediated by the OT receptor present on the A- and B-cells of pancreatic islets [8]. Conversely, administration of insulin increased serum OT level [9]. Combined exposure to insulin and glucose can elicit OT release via their effect on the insulin receptor and glucose transporters (GLUT3, GLUT4) localized on the magnocellular neurons of the supraoptic nucleus [10].
Regulation of lipid metabolism by OT was studied in animals. In lactating buffaloes OT increased serum glucose, triglycerides and cholesterol, and lowered HDL-cholesterol [11]. Conversely, oleoylethanolamide (OEA), synthesized in the small intestine after fat ingestion, stimulated OT synthesis in hypothalamus and reduced food intake [12], [13]. Moreover, OT stimulated beta-oxidation of fatty acids and increased energy expenditure [3].
Some studies suggested that OT regulates vascular tone and natriuresis [14]. Conversely, hypertonic volume expansion induced OT secretion [15]. Thus, OT may also contribute to the regulation of body fluid volume and of blood pressure.
Thus, OT seems to be involved in biological phenomena belonging to the metabolic syndrome (MetS). In addition, OT interacts with secretion and signaling of leptin which is involved in the regulation of energy metabolism [16]. Therefore, our aim was to assess the association between serum OT levels and MetS in older men accounting for other factors associated with MetS and supposed to influence the investigated relationship (e.g. sex steroids, vitamin D, lifestyle factors).
Section snippets
The MINOS cohort
The MINOS study is a prospective single center cohort study of osteoporosis that included men aged 50–85 years [17]. It is a collaborative project involving INSERM and Société de Secours Minière de Bourgogne (SSMB), a large local health insurance company, covering mineworkers and their families living in Greater Montceau-les-Mines (≈35,000 inhabitants). The study was accepted by the ethics committee and performed according to the Declaration of Helsinki as revised in 1983. The cohort was
Oxytocin, body fat and MetS components
The characteristics of the 540 men were as follows: average age 65 ± 7 years, average weight 80 ± 13 kg. Seventy men (13%) were current smokers, 79 men (16%) self-reported ischemic heart disease. Men who had higher OT levels were heavier (Table 1). They had higher prevalence of hypertension, diabetes mellitus and MetS as well as higher serum leptin levels.
In the multivariate models, weight, BMI, total fat and fraction, central and appendicular fat, and waist circumference increased across the OT
Discussion
In this cohort of older men, higher OT levels were associated with higher odds of MetS. The association remained significant after adjustment for confounders. High OT levels were associated with MetS independently of the levels of testosterone or 25OHD. Moreover, the men with high OT and low OC levels had higher odds of MetS.
OT inhibits food intake, increases energy expenditure and produces weight loss [2], [3]. OT-deficient and OT receptor-deficient mice develop obesity [4]. On the one hand,
Funding
This study was supported by a grant from INSERM/Merck Sharp & Dohme Chibret, France and by “Programme Hospitalier de Recherche Clinique InterRégional – Interrégion Sudméditerrannée – 2011” of the French Ministry of Health.
Clinical Trials.gov identifier: NCT01192893.
Author contribution
PS researched data, was responsible for the MINOS study over its entire duration, made most of the statistical analyses and wrote the manuscript. EZA performed the measurements of oxytocin and leptin, as well as contributed to the data interpretation and to the discussion. AV was responsible for the measurements of biological parameters of the metabolic syndrome. PPF performed the measurements of oxytocin and leptin, as well as contributed to the data interpretation and the discussion. EF
Conflict of interest
All the authors declare that they have no conflict of interest as concerns this manuscript.
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