Omega 3 rich diet modulates energy metabolism via GPR120-Nrf2 crosstalk in a novel antioxidant mouse model

Abstract

With obesity rates reaching epidemic proportions, more studies concentrated on reducing the risk and treating this epidemic are vital. Redox stress is an important metabolic regulator involved in the pathophysiology of cardiovascular disease, Type 2 diabetes, and obesity. Oxygen and nitrogenderived free radicals alter glucose and lipid homeostasis in key metabolic tissues, leading to increases in risk of developing metabolic syndrome. Oxidants derived from dietary fat differ in their metabolic regulation, with numerous studies showing benefits from a high omega 3 rich diet compared to the frequently consumed "western diet" rich in saturated fat. Omega 3 (OM3) fatty acids improve lipid profile, lower inflammation, and ameliorate insulin resistance, possibly through maintaining redox homeostasis. This study is based on the hypothesis that altering endogenous antioxidant production and/or increasing OM3 rich diet consumption will improve energy metabolism and maintain insulin sensitivity. We tested the comparative metabolic effects of a diet rich in saturated fat (HFD) and an omega 3-enriched diet (OM3) in the newly developed 'stress-less' mice model that overexpresses the endogenous antioxidant catalase. Eight weeks of dietary intervention showed that mice overexpressing endogenous catalase compared to their wildtype controls when fed an OM3 enriched diet, in contrast to HFD, activated GPR120-Nrf2 crosstalk to maintain balanced energy metabolism, normal circadian rhythm, and insulin sensitivity. These findings suggest that redox regulation of GPR120/FFAR4 might be an important target in reducing risk of metabolic syndrome and associated diseases.

Effect of Docosahexaenoic Acid (DHA) at the Enteric Level in a Synucleinopathy Mouse Model

“…In addition to regulation by GLP-1R, evidence suggests that ω-3 PUFAs, such as DHA, could activate Nrf2-ARE signaling directly [96][97][98]. Moreover, recent studies propose that the activation of GPR120 could increase Nrf2 levels [99,100]. Furthermore, greater nigral dopaminergic neuron loss and more prominent dystrophic dendrites are found in Nrf2 knockout animals following αSyn injection in the ventral midbrain [101].…”

Normal and Pathological NRF2 Signalling in the Central Nervous System

“…Interestingly, NRF2 activity can be modified by daily consumption of specific food and phytochemicals. Most of these micronutrients/compounds are contained in plant-based food such as kaempferol (a polyphenol found in some fruits and vegetables), niga-ichigoside (a triterpenoid saponin from rosacea), salacia chinensis extracts (a climbing plant that contains triterpenes, phenolic compounds, and glycosides), hydroxytyrosol (the main phenolic compound in olives), curcumin, rebaudioside (a sweetener from Stevia rebaudiana), chicoric acid, and omega 3 and polyunsaturated fatty acids [ 170 , 171 , 172 , 173 , 174 , 175 , 176 , 177 , 178 ]. In addition, NFE2L2 gene expression can be upregulated by fibre-enriched diets [ 179 ].…”

Circadian rhythms affect bone reconstruction by regulating bone energy metabolism

“…Studies by Ik Dong Yoo et al have shown that overexpression of Clock and Bmal1 significantly inhibited aerobic sulfation and lactic acid production by reducing the protein expression levels of hexokinase 1 (HK1) and lactate dehydrogenase A (LDHA) [ 176 ]. Redox stress is an important metabolic regulation factor [ 177 ]. Circadian rhythm disorders alter a variety of proteins that are known to regulate glucose stability and/or energy metabolism and are involved in changes in metabolic physiology.…”