Anthocyanidins promotes beiging of white adipose tissue in mice fed a high fat diet via regulation of mitochondrial dynamics

M. MARINO; P. I. OTEIZA; C. RODRIGUEZ LANZI; C. G. FRAGA; E. CREMONINI; D. E. IGLESIAS

Kobe

Congreso; 9th International Conference on Polyphenols and Health; 2019

ICPH

Background: WHO reported that since 1975 obesity has nearly tripled worldwide. Adiposity associated with obesity leads to inflammation and development of pathologies, including type 2 diabetes (T2D) and non alcoholic fatty liver disease (NAFLD). Mitochondria play an essential role in nutrient adaptation. Upon excess nutrient availability, the bioenergetics function of mitochondria is linked to a change of mitochondria architecture, which is associated with afragmented mitochondrial network (fission) and elongated mitochondria (fusion), respectively. Mitochondrial dysfunction leads to adipocyte death, inflammation of white adipose tissue (WAT) and whitening of brown adipose tissue (BAT). Conversion of WAT, especially subcutanoeus fat (sWAT), into BAT, in a process called ?beiging of white adipocytes? can mitigate the developmentof obesity, T2D and NAFLD.Objective: To investigate the capacity of an anthocyanidin (cyanidin and delphinidin)-rich extract (AC) to promote mitochondria biogenesis and beiging of sWAT via regulation of mitochondrial dynamics in mice fed a high fat diet.Material and methods: C57BL/6J mice were divided in 4 groups (10 mice per group) and fed a control diet (10% Kcal from fat), a high fat diet (HF) (60% Kcal from fat) and either the control or HF diets supplemented with 40 mg AC/kg body weight (CA and HFA, respectively) for 14 weeks. Metabolic parameters were measured in plasma. Fat pads were isolated and weighed. sWAT was stained with hematoxylin and eosin (H&E) and the diameter of the adipocytes was measured.Mitochondria morphology and number were evaluated by transmission electron microscopy (TEM). Pathways involved in mitochondriogenesis and mitochondrial dynamics were measured.Results: Consumption of the high fat diet for 14 w led to obesity, steatosis and insulin resistance which were mitigated by AC supplementation. While sWAT weight was similar between HF and HFA groups, AC supplementation significantly decreased adipocyte diameter compared to HF mice. H&E staining showed images compatible with beiging in both AC-treated groups. TEM showed: i) fewer number of mitochondria in HF but not in HFA mice, ii) altered sWAT mitochondria morphology, with a large number of elongated mitochondria, in HF compared to theother groups. These findings were confirmed by measuring the expression of mitochondrial protein markers. AC also prevented HF-mediated inhibition of the pathway leading to mitochondria biogenesis (PPARγ, PRDM16, PGC-1α), and thermogenic respiration (UCP-1). Regarding mitochondrial dynamics, p-Drp1/Drp1, Parkin and NIX levels were markedly lower in HF sWAT, which were prevented by AC supplementation.Conclusion: Consumption of select AC could be an important strategy to mitigate HF-induced obesity and of its co-morbidities via activation of adipocyte mitochondriogenesis and beiging, and through the regulation of mitochondrial dynamics.Keywords: anthocyanins; mitochondriogenesis; mitochondria dynamic; high fat diet; obesity