Title : Indicaxanthin from opuntia ficus indica fruit ameliorates glycidic metabolism and counteracts insulin resistance in high-fat-diet-fed mice
Dysmetabolic conditions related to insulin-resistance (IR) are amongst the most common cause of death globally and their primary prevention has become a compelling goal of public health-oriented strategies. In recent years, there has been a growing interest in those natural, dietary, bioactive compounds able to improve “metabolic health” and reduce cardiovascular risk at population-level. Despite the explosive research interest in the development of novel chemicals to treat IR, its prevalence and associated complications remains extremely high, underlying the unmet and urgent need for novel candidates with sufficient effectiveness.
Indicaxanthin (Ind), a betalain pigment from Opuntia ficus indica fruit has been the object of sound research over the last 20 years. Explored, at first, for its mere antioxidant potential, Ind has been reported to interfere with redox- dependent signalling pathways, exerting significant anti-oxidative and anti-inflammatory effects both in vivo and in vitro. Along these lines and taking into account the strict interconnections between inflammation, oxidative stress and IR, this work has explored whether Ind extracted from Opuntia ficus indica fruit, could exert protective effects in an in vivo model of metabolic disorder related to IR.
To this end, Ind was purified as detailed in the Italian Patent Application No. 102021000015167 filed on 10.06.2021. C57BL/6J mice (n=24) were grouped as follows: 1. a negative control group was fed with a standard diet for 14 weeks; 2. a positive control group was fed with a high fat diet (HFD) for 14 weeks; 3. an Ind-group was fed with HFD for 10 weeks and subsequently received Ind per os at a nutritionally relevant dose of 0.86 mg/kg/day for 4 weeks with a HFD regimen. Body weight, food intake, fat mass, glucose metabolism-related parameters, inflammatory and oxidative status in liver and adipose tissue were compared among the different animal groups. To this end, biochemical, histological, western blotting and RT-PCR analysis were employed.
Our results clearly show that Ind-treatment significantly reduced body weight, daily food intake, visceral and subcutaneous fat mass, and visceral adipose tissue hypertrophy. More interestingly, Ind-administration brought about remarkable, beneficial effects on HFD-induced glucose dysmetabolism. A significant reduction of fasting glycaemia, an improvement of both glucose tolerance and sensitivity to exogenous insulin was, indeed, observed in the Ind- group. Coherently, Ind-treatment decreased plasma fasting insulinaemia and IR as evaluated by the reduction of the homeostatic model assessment index.
From a mechanistic perspective, Ind-mediated effects on HFD-induced glucose dysmetabolism were associated with a reduction of tissue oxidative stress and inflammation. Indeed, a decrease of reactive oxygen and nitrogen species, malondialdehyde and NO levels in both visceral adipose tissue and liver of the Ind-group was observed. In the same tissues, Ind-treatment significantly induced a reduction of TNF-a, CCl-2, F4-80 gene expression and p65, p-JNK, COX-2, i-NOS protein levels. Coherently, a decrease of adipose tissue crown-like structures and hepatic inflammatory foci was detected in the Ind-group.
As a whole, our present results indicate that Ind treatment is able to counteract IR in an in vivo model of metabolic syndrome via anti-oxidative and anti-inflammatory mechanisms, at a nutritionally relevant dose. In perspective, our data suggest a potential employment of the phytochemical, alone or in combo-therapy, to prevent and treat metabolic disorders related to hyperglycaemia and IR.
Audience Take Away:
- The effectiveness of Indicaxanthin as a novel, combotherapeutic agent against insulin resistance.
- Relevant information for biochemists, diabetologist, nutritionists, pharmacologists.