Lipoatrophy‐Associated Insulin Resistance and Hepatic Steatosis are Attenuated by Intake of Diet Rich in Omega 3 Fatty Acids. Issue 7 (3rd February 2020)

• Record Type: Journal Article
• Authors: Moreira, Rafael J.; Castro, Érique; Oliveira, Tiago E.; Belchior, Thiago; Peixoto, Albert S.; Chaves‐Filho, Adriano B.; Moreno, Mayara F.; Lima, Janayna D.; Yoshinaga, Marcos; Miyamoto, Sayuri; Morais, Mychel R. P. T.; Zorn, Telma M. T.; Cogliati, Bruno; Iwai, Leo K.; Palmisano, Giuseppe; Cabral, Fernanda J.; Festuccia, William
• Is Part Of: Molecular nutrition & food research. Volume 64:Issue 7(2020)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2020-02-03
• Subjects: inflammation -- insulin resistance -- lipoatrophy -- nonalcoholic fatty liver disease -- omega 3 fatty acids; Food -- Biotechnology -- Periodicals; Food -- Microbiology -- Periodicals; Nutrition -- Periodicals; Food -- Toxicology -- Periodicals; Nutrition -- Periodicals; Food Microbiology -- Periodicals; Food Technology -- Periodicals; Molecular Biology -- Periodicals; 664.0705
• DOI: 10.1002/mnfr.201900833
• Languages: English
• ISSNs: 1613-4125

Abstract

Abstract : Scope: Glucose homeostasis and progression of nonalcoholic fatty liver disease (NAFLD) and hepatomegaly in severe lipoatrophic mice and their modulation by intake of a diet rich in omega 3 ( n ‐3) fatty acids (HFO) are evaluated. Methods and results: Severe lipoatrophic mice induced by PPAR‐γ deletion exclusively in adipocytes (A‐PPARγ KO) and littermate controls (A‐PPARγ WT) are evaluated for glucose homeostasis and liver mass, proteomics, lipidomics, inflammation, and fibrosis. Lipoatrophic mice are heavier than controls, severely glucose intolerant, and hyperinsulinemic, and develop NAFLD characterized by increased liver glycogen, triacylglycerol, and diacylglycerol contents, mitotic index, apoptosis, inflammation, steatosis score, fibrosis, and fatty acid synthase (FAS) content and activity. Lipoatrophic mice also display liver enrichment with monounsaturated in detriment of polyunsaturated fatty acids including n‐3 fatty acids, and increased content of cardiolipin, a tetracyl phospholipid exclusively found at the mitochondria inner membrane. Administration of a high‐fat diet rich in n ‐3 fatty acids (HFO) to lipoatrophic mice enriches liver with n ‐3 fatty acids, reduces hepatic steatosis, FAS content and activity, apoptosis, inflammation, and improves glucose homeostasis. Conclusion: Diet enrichment with n‐3 fatty acids improves glucose homeostasis and reduces liver steatosis and inflammation without affecting hepatomegaly in severe lipoatrophic mice. Abstract : Intake of a high‐fat diet rich in omega 3 polyunsaturated ( n ‐3) fatty acids reduces hepatic de novo lipogenesis, steatosis, apoptosis, and inflammation, and improves glucose homeostasis in lipoatrophic mice. These findings support the notion that diet enrichment with n ‐3 fatty acids is an effective strategy to protect liver from lipotoxicity and improve metabolic complications associated with severe lipoatrophy in mice.