Effects of Long-Term DHA Supplementation and Physical Exercise on Non-Alcoholic Fatty Liver Development in Obese Aged Female Mice

• Published in: Nutrients Vol. 13; no. 2; p. 501
• Main Authors: Yang, Jinchunzi, Sáinz, Neira, Félix-Soriano, Elisa, Gil-Iturbe, Eva, Castilla-Madrigal, Rosa, Fernández-Galilea, Marta, Martínez, J Alfredo, Moreno-Aliaga, María J
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01-02-2021; MDPI
• Subjects: Aging; Aging - physiology; Animals; Autophagy; Autophagy - genetics; Autophagy - physiology; Catabolism; Diet, High-Fat; Disease Models, Animal; Docosahexaenoic acid; Docosahexaenoic Acids - administration & dosage; Endoplasmic reticulum; Endoplasmic Reticulum Stress - genetics; Exercise; Fatty liver; Female; Gene expression; Gene Expression Regulation - drug effects; Gene Expression Regulation - physiology; Genes; High fat diet; Inflammation; Inflammation - genetics; Interleukin 6; Kinases; Lipid Metabolism; Lipids; lipogenesis; Lipogenesis - genetics; Liver; Liver - chemistry; Liver - metabolism; Liver diseases; Mice; Mice, Inbred C57BL; non-alcoholic fatty liver; Non-alcoholic Fatty Liver Disease - etiology; Non-alcoholic Fatty Liver Disease - genetics; Non-alcoholic Fatty Liver Disease - prevention & control; Obesity; Obesity - complications; Obesity - etiology; Omega-3 fatty acids; Oxidation; Phagocytosis; Physical Conditioning, Animal - physiology; Physical exercise; RNA, Messenger - analysis; Steatosis; TLR4 protein; Toll-like receptors; Transcription activation; Treadmills; Unsaturated fatty acids; Spain; United States > US; autophagy; non-alcoholic fatty liver; inflammation; ER stress; exercise; lipogenesis; omega-3 fatty acids; aging; fatty acid oxidation; obesity
• ISSN: 2072-6643; 2072-6643
• DOI: 10.3390/nu13020501

Obesity and aging are associated to non-alcoholic fatty liver disease (NAFLD) development. Here, we investigate whether long-term feeding with a docosahexaenoic acid (DHA)-enriched diet and aerobic exercise, alone or in combination, are effective in ameliorating NAFLD in aged obese mice. Two-month-old female C57BL/6J mice received control or high fat diet (HFD) for 4 months. Then, the diet-induced obese (DIO) mice were distributed into four groups: DIO, DIO + DHA (15% dietary lipids replaced by a DHA-rich concentrate), DIO + EX (treadmill running), and DIO + DHA + EX up to 18 months. The DHA-rich diet reduced liver steatosis in DIO mice, decreasing lipogenic genes (
, and upregulated lipid catabolism genes (
/
) expression. A similar pattern was observed in the DIO + EX group. The combination of DHA + exercise potentiated an increase in
and
genes, and AMPK activation, key regulators of fatty acid oxidation. Exercise, alone or in combination with DHA, significantly reversed the induction of proinflammatory genes (
,
) in DIO mice. DHA supplementation was effective in preventing the alterations induced by the HFD in endoplasmic reticulum stress-related genes (
) and autophagy markers (LC3II/I ratio, p62,
). In summary, long-term DHA supplementation and/or exercise could be helpful to delay NAFLD progression during aging in obesity.