Abstract
The human cytokine interleukin (IL)-37 is an anti-inflammatory member of the IL-1 family of cytokines. Transgenic expression of IL-37 in mice protects them from diet-induced obesity and associated metabolic complications including dyslipidemia, inflammation and insulin resistance. The precise mechanism of action leading to these beneficial metabolic effects is not entirely known. Therefore, we aimed to assess in detail the effect of transgenic IL-37 expression on energy balance, including food intake and energy expenditure. Feeding homozygous IL-37 transgenic mice and wild-type (WT) control mice a high-fat diet (HFD; 45% kcal palm fat) for 6 weeks showed that IL-37 reduced body weight related to a marked decrease in food intake. Subsequent mechanistic studies in mice with heterozygous IL-37 expression versus WT littermates, fed the HFD for 18 weeks, confirmed that IL-37 reduces food intake, which led to a decrease in lean body mass, but did not reduce fat mass and plasma lipid levels or alterations in energy expenditure independent of lean body mass. Taken together, this suggests that IL-37 reduces lean body mass by reducing food intake.
Highlights
The worldwide prevalence of obesity, defined as a body mass index (BMI) >30 kg/m2, has nearly doubled since 1980, and at least 2.7 million people die each year as a result of obesity [1]
Body weight of the IL-37tg mice was already 3.6 g lower compared to the WT control mice before initiation of the high-fat diet (HFD) (Figure 1A) and this difference was magnified during HFD feeding resulting in a body weight difference of 10.5 g after 6 weeks of HFD (p < 0.001)
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Summary
The worldwide prevalence of obesity, defined as a body mass index (BMI) >30 kg/m2, has nearly doubled since 1980, and at least 2.7 million people die each year as a result of obesity [1]. Obesity is caused by a positive energy balance that leads to excessive fat accumulation in adipose tissue, hypertrophy of adipocytes, hypoxia, and in the end cell death. This results in recruitment of inflammatory cells by white adipose tissue (WAT), which eventually leads to adipose tissue dysfunction, preceding dyslipidemia and type 2 diabetes [4,5]. It was shown that IL-37 suppresses expression of pro-inflammatory factors in monocytes and macrophages [10,17] These studies indicate that IL-37 expression counteracts pro-inflammatory cytokine expression through controlled mechanisms that ensure balance between host defense functions of inflammation and adverse effects [10,16,17]
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