Abstract

Globin digest (GD), a bioactive oligopeptide derived from porcine hemoglobin proteins, has been demonstrated to have beneficial effects on improving postprandial hyperlipidemia, hyperglycemia, and liver injury. We previously reported the lipid-lowering effects of GD using a zebrafish obesogenic test. Here, we sought to evaluate the effect of GD on visceral adiposity and the underlying molecular mechanisms using zebrafish and mouse obesity models. GD ameliorated dyslipidemia and suppressed the accumulation of visceral adipose tissue (VAT) in adult obese zebrafish. Transcriptomic analysis by RNA sequencing of GD-treated adult zebrafish revealed that GD upregulated UCP1-related pathways. Further, we performed mouse experiments and found that GD intake (2 mg/g body weight/day) was associated with lowered plasma triglyceride and total cholesterol levels, decreased VAT accumulation, and improved adipocyte hypertrophy with the upregulation of Ucp1 expression in white adipose tissue at both the mRNA and protein levels. Taken together, these results indicate that GD improves visceral adiposity by upregulating UCP1 expression, providing a novel perspective on combating obesity.

Highlights

  • Obesity is becoming a significant global public health issue due to rapid increases in its prevalence and consequent health threats

  • Zebrafish in the Globin digest (GD) group were fed with a normal diet supplemented with 10% GD-containing food for 2 weeks, followed by 1 week of overfeeding and a continuous GD-containing diet

  • As the zebrafish model is a powerful tool for anti-obesity drug discovery, we used juvenile zebrafish for test material screening and adult diet-induced obese zebrafish to assess the hit materials

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Summary

Introduction

Obesity is becoming a significant global public health issue due to rapid increases in its prevalence and consequent health threats. According to the most recent fact sheet published by the World Health Organization, >1.9 billion adults were overweight, and of these, > 650 million were obese in 2016 [1]. Data involving prevalence in the generation showed that > 378 million children under the age of 19 were overweight or obese, which has risen > 4-fold from 1975 to 2016. Excess energy is mainly stored in white adipose tissue (WAT) as triglycerides [4]. Another type of adipose tissue, brown adipose tissue (BAT), functions to dissipate energy as heat through uncoupling protein-1 (UCP1) [5,6,7]. WAT can transform into the BAT phenotype in response to appropriate stimuli, which are primarily mediated

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