Abstract

ObjectiveWe have previously shown that bitter melon seed oil (BMSO), which is rich in cis-9, trans-11, trans-13 conjugated linolenic acid, is more potent than soybean oil in attenuating body fat deposition in high-fat diet-induced obese C57BL/6J mice. The aim of this study was to obtain a comprehensive insight into how white adipose tissue (WAT) is affected by BMSO administration and to explore the underlying mechanisms of the anti-adiposity effect of BMSO.Methods and ResultsA proteomic approach was used to identify proteins differentially expressed in the WAT of mice fed diets with or without BMSO for 11 wks. The WAT was also analyzed histologically for morphological changes. Two-dimensional gel electrophoresis (pH 4–7) revealed 32 spots showing a statistically significant difference (P<0.05) in intensity in BMSO-treated mice and 30 of these were shown to code for 23 proteins (15 increased and 8 decreased expression; >2-fold change). Combined with histological evidence of macrophage infiltration and brown adipocyte recruitment, the proteomic and immunoblotting data showed that the WAT in mice subjected to long-term high dose BMSO administration was characterized by reduced caveolae formation, increased ROS insult, tissue remodeling/repair, mitochondria uncoupling, and stabilization of the actin cytoskeleton, this last change being putatively related to an increased inflammatory response.ConclusionThe anti-adiposity effect of BMSO is associated with WAT delipidation, inflammation, and browning. Some novel proteins participating in these processes were identified. In addition, the BMSO-mediated WAT browning may account for the increased inflammation without causing adverse metabolic effects.

Highlights

  • Obesity has become a worldwide epidemic and is causally linked with many metabolic disorders and cancers [1]

  • The bitter melon seed oil (BMSO)-mediated white adipose tissue (WAT) browning may account for the increased inflammation without causing adverse metabolic effects

  • Histochemical Study With energy intake controlled to be equal, the body fat in the LBM, MBM, and HBM groups was significantly reduced, respectively, by 38, 42, and 73% compared to the HS control, and this dosedependent reduction in adiposity was supported by changes in the serum leptin concentration [11]

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Summary

Introduction

Obesity has become a worldwide epidemic and is causally linked with many metabolic disorders and cancers [1]. Many reports have shown that conjugated fatty acids, i.e. polyunsaturated fatty acids with a conjugated diene or triene, are less adipogenic than non-conjugated fatty acids and might be helpful in weight reduction [2,3,4,5,6]. Of these, conjugated linoleic acid (CLA), with an anti-adipogenic effect mainly attributed to the trans-10, cis-12 (t10, c12)- isomer, has been the most studied functionally and mechanistically. In mice, t10, c12-CLA alone or a t10, c12-CLA and c9, t11-CLA mixture elicits lipodystrophy with comorbidity of insulin resistance and hepatic steatosis, which raises concerns for human application [2,3]. Commercial CLA, a 1:1 mixture of c9, t11-CLA and t10, c12-CLA, is chemically synthesized. We examined the effects of the natural product, cis-9, trans-11, trans-13-conjugated linolenic acid (c9,t11,t13-CLN), otherwise known as a-eleostearic acid, which is abundantly present in bitter melon

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