Metabolic Cytokines at Fasting and During Macronutrient Challenges: Influence of Obesity, Female Androgen Excess and Sex.

M Ángeles Martínez-García,Samuel Moncayo,Manuel Luque-Ramírez,Francisco Álvarez-Blasco,María Insenser,Héctor F Escobar-Morreale

doi:10.3390/nu11112566

Abstract

Scope: Cytokines have pleiotropic functions within the organism and their levels may be influenced by obesity, visceral adiposity and sex hormones. Diet composition may also affect their systemic concentrations during fasting and in the postprandial period. Hence, we studied the influence of sex steroids and obesity on the circulating levels of a panel of metabolic cytokines in the fasting state and after single macronutrient challenges. Methods: On alternate days we submitted 17 women with polycystic ovary syndrome (PCOS) (9 non-obese, 8 obese), 17 non-hyperandrogenic control women (9 non-obese, 8 obese) and 19 control men (10 non-obese, 9 obese) to isocaloric oral glucose, lipid and protein loads. Serum levels of omentin-1, vaspin, lipocalin-2, adipsin, PAI-1, chemerin, FGF-21 and FGF-23 were determined by Luminex multiplex technology. Results: During fasting, obese patients presented higher levels of PAI-1, chemerin and adipsin but decreased FGF-23 and omentin-1 compared with non-obese subjects. Vaspin showed sexual dimorphism with lower levels in men than women with PCOS and female controls. Following macronutrient ingestion, most metabolic cytokines presented a similar physiological response consisting of a decrease in circulating concentrations, which was inversely associated with the fasting levels of these molecules. Protein intake caused the major postprandial decrease whereas glucose did not significantly reduce PAI-1, FGF-23 and vaspin, and even increased FGF-21. Regardless of the macronutrient administered, vaspin levels showed a larger reduction in non-obese individuals while the decrease in PAI-1 was particularly noticeable in the obese subgroup. The postprandial reductions of omentin-1 and FGF-23 after glucose and protein loads were influenced by obesity. No major differences were found between patients with PCOS and male and female controls. Conclusions: Obesity, but not PCOS or sex, markedly influences metabolic cytokine levels at fasting and after macronutrient ingestion. The observed postprandial decrease in their circulating concentrations might represent a physiological compensatory mechanism against food-induced inflammation and oxidative stress. This mechanism is altered by obesity and is differently modulated by macronutrients, suggesting a larger contribution of glucose to stressful postprandial responses.

Highlights

Cytokines have pleiotropic functions within the organism including the modulation of immune inflammatory responses and the regulation of food intake and energy balance by acting in the central nervous system and in peripheral tissues [1]
Patients with polycystic ovary syndrome (PCOS) presented both clinical and biochemical hyperandrogenism but did not show higher waist circumference (WC), waist to hip ratio (WHR) or differences in metabolic parameters when compared with control women
WC and WHR but lower levels of high-density lipoprotein cholesterol (HDL) and sex hormone-binding globulin (SHBG) compared with both groups of women

Summary

Introduction

Cytokines have pleiotropic functions within the organism including the modulation of immune inflammatory responses and the regulation of food intake and energy balance by acting in the central nervous system and in peripheral tissues [1] These metabolic hormones are produced in diverse organs and tissues such as adipose, liver and bone that secrete adipokines and related molecules with critical roles in inflammation, insulin sensitivity and carbohydrate and lipid metabolism. Circulating adipokine concentrations—both in the fasting state and after an oral glucose challenge—are influenced by weight excess and by abdominal obesity, sex and sex hormones [4,5] In this regard, patients with polycystic ovary syndrome (PCOS), which is the most prevalent endocrine and metabolic disorder in premenopausal women [6], may present different cytokine levels compared with non-hyperandrogenic women [7]. As other individuals with adipose tissue and metabolic dysfunction, PCOS patients manifest postprandial dysmetabolism—a sustained elevation of carbohydrates and lipids in the postprandial period [9]—that has been associated with impaired cytokine secretion [10]

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Conclusion