Abstract

Obesity-related dysmetabolic conditions are amongst the most common causes of death globally. Indicaxanthin, a bioavailable betalain pigment from Opuntia ficus-indica fruit, has been demonstrated to modulate redox-dependent signalling pathways, exerting significant anti-oxidative and anti-inflammatory effects in vitro and in vivo. In light of the strict interconnections between inflammation, oxidative stress and insulin resistance (IR), a nutritionally relevant dose of indicaxanthin has been evaluated in a high-fat diet (HFD) model of obesity-related IR. To this end, biochemical and histological analysis, oxidative stress and inflammation evaluations in liver and adipose tissue were carried out. Our results showed that indicaxanthin treatment significantly reduced body weight, daily food intake and visceral fat mass. Moreover, indicaxanthin administration induced remarkable, beneficial effects on HFD-induced glucose dysmetabolism, reducing fasting glycaemia and insulinaemia, improving glucose and insulin tolerance and restoring the HOMA index to physiological values. These effects were associated with a reduction in hepatic and adipose tissue oxidative stress and inflammation. A decrease in RONS, malondialdehyde and NO levels, in TNF-α, CCL-2 and F4-80 gene expression, in p65, p-JNK, COX-2 and i-NOS protein levels, in crown-like structures and hepatic inflammatory foci was, indeed, observed. The current findings encourage further clinical studies to confirm the effectiveness of indicaxanthin to prevent and treat obesity-related dysmetabolic conditions.

Highlights

  • Introduction published maps and institutional affilObesity is a major, global health problem, affecting approximately 500 million adults and 40 million children worldwide [1]

  • Adipocyte diameter and area in high-fat diet (HFD) mice were significantly higher than those in STD mice; the degree of increase was significantly reduced in indicaxathintreated mice, suggesting that indicaxanthin decreases the adipose tissue hypertrophy (Figure 2A–C)

  • The analysis of frequency distribution confirmed this result, revealing that adipocyte sizes in visceral adipose tissue from STD and HFD mice were shifted towards smaller adipocytes after indicaxanthin treatment and the proportion of large adipocytes was reduced (Figure 2D)

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Summary

Introduction

Introduction published maps and institutional affilObesity is a major, global health problem, affecting approximately 500 million adults and 40 million children worldwide [1]. Prospective studies highlight that obesity increases the risk of several pathological conditions, such as type-2 diabetes (DM), hypertension and coronary heart disease, being responsible for almost 3 million deaths every year [2]. Due to its spectacular complexity, as both a nutrient sink and endocrine organ, adipose tissue is a key district where metabolic regulations and immunological responses are highly integrated and the proper function of each depends on the other. Along these lines, an obesity-induced disruption of this delicate equilibrium results in the development of inflammatory-dependent, dysmetabolic conditions, including insulin resistance (IR), DM and non-alcoholic fatty liver disease (NAFLD) [3]. An obesity-induced disruption of this delicate equilibrium results in the development of inflammatory-dependent, dysmetabolic conditions, including insulin resistance (IR), DM and non-alcoholic fatty liver disease (NAFLD) [3]. iations.

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