Abstract

CD24 is a glycophosphatidylinositol (GPI)-linked cell surface receptor that is involved in regulating the survival or differentiation of several different cell types. CD24 has been used to identify pre-adipocytes that are able to reconstitute white adipose tissue (WAT) in vivo. Moreover, we recently found that the dynamic upregulation of CD24 in vitro during early phases of adipogenesis is necessary for mature adipocyte development. To determine the role of CD24 in adipocyte development in vivo, we evaluated the development of the inguinal and interscapular subcutaneous WAT and the epididymal visceral WAT in mice with a homozygous deletion of CD24 (CD24KO). We observed a significant decrease in WAT mass of 40% to 74% in WAT mass from both visceral and subcutaneous depots in male mice, with no significant effect in female mice, compared to wild-type (WT) sex- and age-matched controls. We also found that CD24KO mice had increased fasting glucose and free fatty acids, decreased fasting insulin, and plasma leptin. No major differences were observed in the sensitivity to insulin or glucose, or in circulating triglycerides, total cholesterol, HDL-cholesterol, or LDL-cholesterol levels between WT and CD24KO mice. Challenging the CD24KO mice with either high sucrose (35%) or high fat (45%) diets that promote increased adiposity, increased WAT mass and fasting insulin, adiponectin and leptin levels, as well as reduced the sensitivity to insulin and glucose, to the levels of WT mice on the same diets. The CD24-mediated reduction in fat pad size was due to a reduction in adipocyte cell size in all depots with no significant reduction pre-adipocyte or adipocyte cell number. Thus, we have clearly demonstrated that the global absence of CD24 affects adipocyte cell size in vivo in a sex- and diet-dependent manner, as well as causing metabolic disturbances in glucose homeostasis and free fatty acid levels.

Highlights

  • Obesity, caused by excessive caloric intake and exacerbated by both environmental and genetic factors [1], is an increase in the amount of white adipose tissue (WAT) to pathological levels

  • We found that male CD24 knock-out (CD24KO) had significantly less overall fat and percentage body fat with a difference that increased over time when compared to age and sex-matched wild-type (WT) control mice (Fig 1A and 1B)

  • In the estimate of total body weight derived from the DEXA scans, we found that the mice had similar weights at 5 and 9 weeks of age, which diverged by 12 weeks with CD24KO mice weighing 91±6% of their WT counterparts at that age (Fig 1G)

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Summary

Introduction

Obesity, caused by excessive caloric intake and exacerbated by both environmental and genetic factors [1], is an increase in the amount of white adipose tissue (WAT) to pathological levels. Lipodystrophy is either a generalized or localized loss of WAT induced by genetic or environmental factors [2]. In both situations the increased circulation of lipotoxic free fatty acids (FFA) and the reduced ability to regulate blood glucose levels promotes co-morbidities such as diabetes, stroke, and cardiovascular disease. WAT stores excess energy in the form of triglycerides (TG), as well as being an endocrine organ that secretes appetite regulating hormones such as adiponectin and leptin [3]. Mature adipocytes in WAT are composed of a unilocular lipid droplet (LD), and a thin ring of cytoplasm with a flattened nucleus [4]

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