Sex-based differences in phagocyte metabolic profile in rats with monosodium glutamate-induced obesity

Abstract

The important component of obesity pathogenesis is inflammatory activation of innate immune cells within adipose tissue and in other body locations. Both the course of obesity and innate immune reactivity are characterized by sex-associated differences. The aim of the work was a comparative investigation of metabolic profiles of phagocytes from different locations in male and female rats with MSG-induced obesity. The administration of monosodium glutamate (MSG) caused obesity, with sex-associated differences, that was more severe in male rats. Obesity was associated with pro-inflammatory activation of CD14+ phagocytes from adipose tissue in female, but not in male rats, which was demonstrated by decreased phagocytosis activity along with increased ROS generation. Phagocytes from the peritoneal cavity and peripheral blood of obese female rats exhibited neutral metabolic profile, whereas those cells from obese male rats displayed a pro-inflammatory metabolic profile. Thus, the manifestation of obesity-induced inflammation was characterized by different patterns of metabolic profile of phagocytes in male and female rats. Identified immune cell characteristics expand our knowledge of obesity immunobiology and may help to develop more effective preventive and therapeutic interventions for obese patients of different sexes.

Introduction

The worldwide prevalence of obesity and its metabolic complications have substantially increased in recent years1,2. The propensity towards development of obesity differs between the sexes, and this is, first of all, due to the effect of sex hormones on adipocyte metabolism3,4. In addition, sex-associated differences in cell types, other than adipocytes within adipose tissue, such as innate immune cells, also account for differences in obesity between males and females. Sex-based differences in immune responses are well documented. These differences are attributed to the immunomodulatory effects of sex hormones, as well as being related to the X chromosome gene contributions. The X chromosome encodes for a number of critical genes involved in the regulation of immunity, such as Toll-like receptors. Moreover, the X chromosome contains about 10% of all microRNAs in the genome, which regulate immune cell differentiation and functioning5,6. The sex differential expression of PRRs stipulates sex-specific activity of the innate immune cells following stimulation. Peritoneal phagocytes from female rodents produce higher levels of anti-inflammatory prostanoids, than do male-derived cells in response to microbial stimuli. Whereas, male phagocytes produce more pro-inflammatory cytokines and chemokines following PRR stimulation, than do female cells. The phagocytic activity of innate immune cells from many locations is higher in females than in males7,8,9. Sex hormones exert different immunomodulating effects. Natural level of testosterone shows a significant positive relationship with Th1 immune response, whereas natural level of estrogen – with Th2 immune cell metabolic shift10,11.

Adipose tissue and immune system are closely interrelated. Major alterations of immune responses expressed during obesity, have been represented as obesity-induced low-grade inflammation or «meta-inflammation»12,13. This disorder is associated with an increase in local adipose tissue of inflammatory cytokines and other proteins (TNFα, IL-1b, IL-6, IFNγ, MCP-1,

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