Sexual Dimorphism in Changes That Occur in Tissues, Organs and Plasma during the Early Stages of Obesity Development

Abstract

Despite obesity being a major health concern, information on the early clinical changes that occur in plasma and tissues during obesity development and the influence of sexual dimorphism is lacking. This study investigated changes in tissue and organ histology, macrophage infiltration, plasma hormones, lipid, and chemokine and cytokine levels in mice fed on a high fat diet for 11-weeks. An increase in adiposity, accompanied by adipocyte hypertrophy and macrophage infiltration, was observed to be significantly greater in males than females. Important changes in cell morphology and histology were noted in the lungs, liver, kidney, spleen, and heart, which may indicate early signs for developing obesity associated comorbidities. Leptin, but not adiponectin, was significantly altered during weight gain. Additionally, leptin, but not adiposity, correlated with insulin levels. Interestingly, GM-CSF, TNFα, and IL-12 (p70) were not produced in the early stages of obesity development. Meanwhile, the production of MCP-1, IP-10, RANTES, IL-10, IL-6, KC, and IL-9 were greatly influenced by sexual dimorphism. Importantly, IL-6/IL-10 axis of anti-inflammatory cytokine regulation was observed only in females and may account for their significantly lower weight gain compared to males. This study provides new knowledge on how sexual dimorphism may influence the development of obesity and associated comorbidities.

Slc7a8 Deletion Is Protective against Diet-Induced Obesity and Attenuates Lipid Accumulation in Multiple Organs

“…Renal injury and disease have been associated with obesity, and studies in mice have documented renal morphological changes due to HFD [ 22 , 38 ]. An accumulation of lipid droplets in the kidneys was observed in DIO in WTHFD, suggesting that an increase in body weight could contribute to renal abnormalities.…”

“…Immunohistochemical analysis of macrophages was performed as previously described [ 22 ]. FFPE sections were baked overnight at 54 °C, followed by dewaxing in xylene.…”

Slc7a8 deletion is protective against diet-induced obesity and attenuates lipid accumulation in multiple organs

“…Renal injury and disease have been associated with obesity and studies in mice have documented renal morphological changes due to HFD [30,31]. An increase in glomerular size and accumulation of lipid droplets in the kidneys was observed in DIO in WTHFD, suggesting an increase in body weight could contribute to renal abnormalities.…”

“…Immunohistochemical analysis of macrophages was performed as previously described [31]. Briefly, tissue sections were stained with F4/80 rat anti mouse antibody clone A3-1 (Bio-Rad Laboratories, Sandton, Johannesburg, South Africa).…”

Differences in Inflammatory Cytokine Profile in Obesity-Associated Asthma: Effects of Weight Loss

“…Th9 cells and IL-9 promote accumulation and activation of T cells, ILC2s, mast cells, and eosinophils and increase levels of IL-5, IL-13, and IgE in animal asthma models [110]. IL-9 concentrations have been found significantly elevated in male obese mice but not in female obese mice with respect to lean mice, suggesting that sexual dimorphism influences IL-9 production, with dominant expression in males [111]. In our study, serum levels of IL-9 were higher in obese asthma patients with respect to healthy controls and obese subjects, a finding that suggests that asthma and obesity might have additive effects on IL-9 secretion.…”