No abstract

The Renin Angiotensin System (RAS), a key regulator of blood pressure has been linked to metabolic disorders. We have previously reported that adipose overexpression of angiotensinogen in mice (Agt-Tg) induces obesity, in part mediated by adipose tissue inflammation, through yet unidentified mechanisms. Hence, we hypothesize that adipose tissue enrichment of angiotensinogen leads to activation of inflammatory cascades and endoplasmic reticulum (ER) stress, thereby, contributing to obesity. We used wild type (Wt), Agt-Tg and Agt-knockout (KO) mice along with 3T3-L1 and human adipocytes treated with RAS, ER stress and inflammation inhibitors. ER stress and pro-inflammation markers were significantly higher in Agt-Tg compared to Wt mice and captopril significantly reduced their expression. Furthermore, in vitro treatment with Ang II significantly induced ER stress and inflammation, whereas angiotensin II receptor inhibitor, telmisartan reduced RAS effects. Moreover, miR-30 family had significantly lower expression in Agt-Tg group. MiR-708-5p and -143-3p were upregulated when RAS was overexpressed, and RAS antagonists reduced miR-143-3p and -708-5p in both mouse adipose tissue and adipocytes. Activation of RAS by Ang II treatment, increased inflammation and ER stress in adipocytes mainly via AT1 receptor, possibly mediated by miR-30 family, -708-5p and/or -143-3p. Hence, RAS and mediating microRNAs could be used as potential targets to reduce RAS induced obesity and related comorbid diseases.

Objective Over half of American women of childbearing age have either obesity or overweight. Hence, maternal programming through diet is critical for prevention of diseases in the offspring. Clinical trials with fish oil (FO) report various health benefits; however, it remains unclear whether maternal and postnatal consumption of FO protects offspring from adverse effects of consuming a high‐fat (HF) diet. Methods Female mice were fed HF diets supplemented without (HF) or with FO from 8 weeks before pregnancy through lactation. A low‐fat (LF) diet was included as a control diet. After weaning, male offspring from HF or FO dams were either continued on their respective diet (HF‐HF and FO‐FO) or switched to the other diet (HF‐FO and FO‐HF) and compared with LF. Phenotypic and mechanistic studies were performed. Results FO‐FO offspring demonstrated significantly higher glucose clearance and insulin sensitivity compared with other pups fed the HF diet (P < 0.05). Furthermore, FO‐FO pups had lower adiposity, inflammation, and fat deposition in the liver, consistent with reduced markers of hepatic lipogenesis and increased hepatic lipid oxidation. Conclusions Supplementation of FO during pregnancy and early life is more beneficial than treating with FO either during pregnancy or in pups.