Abstract
Background/objectivesAdipose tissue macrophages (ATMs) exist in either the M1 or M2 form. The anti-inflammatory M2 ATMs accumulate in lean individuals, whereas the pro-inflammatory M1 ATMs accumulate in obese individuals. Bee venom phospholipase A2 (bvPLA2), a major component in honeybee (Apis mellifera) venom, exerts potent anti-inflammatory effects via interactions with regulatory T cells (Treg) and macrophages. This study investigated the effects of bvPLA2 on a high-fat diet (HFD)-induced obesity in mice.Subjects/methodsFor in vivo experiments, male C57BL/6, CD206-deficient, and Treg-depleted mice models were fed either a normal diet 41.86 kJ (ND, 10 kcal% fat) or high-fat diet 251.16 kJ (HFD, 60 kcal% fat). Each group was i.p. injected with PBS or bvPLA2 (0.5 mg/kg) every 3 days for 11 weeks. Body weight and food intake were measured weekly. Histological changes in the white adipose tissue (WAT), liver, and kidney as well as the immune phenotypes of the WAT were examined. Immune cells, cytokines, and lipid profiles were also evaluated. The direct effects of bvPLA2 on 3T3-L1 pre-adipocytes and bone marrow-derived macrophages were measured in vitro.ResultsbvPLA2 markedly decreased bodyweight in HFD-fed mice. bvPLA2 treatment also decreased lipid accumulation in the liver and reduced kidney inflammation in the mice. It was confirmed that bvPLA2 exerted immunomodulatory effects through the CD206 receptor. In addition, bvPLA2 decreased M1 ATM and alleviated the M1/M2 imbalance in vivo. However, bvPLA2 did not directly inhibit adipogenesis in the 3T3-L1 adipose cells in vitro.ConclusionsbvPLA2 is a potential therapeutic strategy for the management of obesity by regulating adipose tissue macrophage homeostasis.
Highlights
Obesity is a growing global health problem that is characterized by the excess accumulation of body fat and a high body mass index (BMI ≥ 30) [1, 2]
After 4 weeks of normal diet (ND) (10.3 kcal/day) or high-fat diet (HFD) (14.0 kcal/day) feeding, Bee venom phospholipase A2 (bvPLA2) or PBS vehicle injection was initiated on week 5 (Fig. 1A)
The weights of the epididymal white adipose tissue (WAT) and inguinal WAT were increased in the HFD group compared to the ND, whereas these weights were significantly decreased in the HFD + Phospholipase A2 (PLA2) group compared to the HFD
Summary
Obesity is a growing global health problem that is characterized by the excess accumulation of body fat and a high body mass index (BMI ≥ 30) [1, 2]. It has been reported that the accumulation of immune cells, such as macrophages, monocytes, and lymphocytes, in adipose tissue (AT) is increased in the obese state. Adipose tissue macrophages (ATMs) have been known to rapidly increase in the early stages of obesity, inducing inflammation and adipocyte apoptosis [10,11,12]. Distinct from sPLA2-V and iPLA2-VIA, bee venom PLA2 (bvPLA2) has exhibited therapeutic effects on Parkinson’s disease, Alzheimer’s disease, pulmonary inflammation, and atopic dermatitis through an increase in the Foxp3+ regulatory T-cell populations (Treg) resulting in reduced inflammation [25,26,27,28]. We investigated the effect of bvPLA2 on macrophage inflammation in a HFDinduced obesity mouse model
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