Abstract

Worldwide rates of Western-diet-induced obesity epidemics are growing dramatically. Being linked with numerous comorbidities and complications, including cardiovascular disease, type 2 diabetes, cancer, chronic inflammation, and osteoarthritis (OA), obesity represents one of the most threatening challenges for modern healthcare. Mouse models are an invaluable tool for investigating the effects of diets and their bioactive components against high fat diet (HFD)-induced obesity and its comorbidities. During recent years, very high fat diets (VHFDs), providing 58–60% kcal fat, have become a popular alternative to more traditional HFDs, providing 40–45% total kcal fat, due to the faster induction of obesity and stronger metabolic responses. This project aims to investigate if the 60% fat VHFD is suitable to evaluate the protective effects of curcumin in diet-induced obesity and osteoarthritis. B6 male mice, prone to diet-induced metabolic dysfunction, were supplemented with VHFD without or with curcumin for 13 weeks. Under these experimental conditions, feeding mice a VHFD for 13 weeks did not result in expected robust manifestations of the targeted pathophysiologic conditions. Supplementing the diet with curcumin, in turn, protected the animals against obesity without significant changes in white adipocyte size, glucose clearance, and knee cartilage integrity. Additional research is needed to optimize diet composition, curcumin dosage, and duration of dietary interventions to establish the VHFD-induced obesity for evaluating the effects of curcumin on metabolic dysfunctions related to obesity and osteoarthritis.

Highlights

  • The global epidemic of obesity represents one of the most urgent healthcare challenges worldwide

  • The anti-inflammatory effects of curcumin relate to its ability to modulate intracellular signaling via the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), activator protein 1 (AP-1), and signal transducer and activator of transcription (STAT) pathways, thereby interfering with the signal transduction of pro-inflammatory transcription factors [3]

  • As feeding mice with very high fat diets (VHFDs) may result in nonalcoholic fatty liver disease (NAFLD), we evaluated the effect of dietary curcumin on fat deposition in the liver

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Summary

Introduction

The global epidemic of obesity represents one of the most urgent healthcare challenges worldwide. The beneficial effects of curcumin against obesity, metabolic disorders, inflammation, malignancies, and a variety of other pathophysiologic conditions have been ascertained in numerous clinical trials [2]. Inhibition of NF-κB may be mediated by the toll-like receptor 4 (TLR-4)-dependent mechanisms [4,5,6]. Recent mouse studies have implicated curcumin in the recovery from Western-diet-induced intestinal barrier permeability [9,10]. It should be noted that, like other polyphenols, curcumin is poorly absorbed in the intestines and undergoes deep biotransformation by intestinal bacteria [11,12,13,14]. Since the relative contribution of curcumin and its metabolites to reported health protective effects has not been evaluated, the molecular mechanisms of these effects require further clarification

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