Endocrine Abstracts

Perinatal maternal high-fat (HF) and isocaloric diet induced obesity and metabolic disorders in the offspring since weaning. At adulthood, oxidative soleus skeletal muscle of HF male offspring exhibited lipid accumulation and mitochondrial damage. At birth, HF offspring have higher n-6:n-3 polyunsaturated fatty acids (PUFA) plasma ratio. We hypothesized that HF offspring´s mitochondria of skeletal muscle exhibit damages at weaning that could be mitigated by fish oil (FO, rich in n-3PUFA) supplementation during pregnancy. Female Wistar rats consumed an isocaloric, control (C: 11% lipids) or high-fat diet (HF: 29% lipids) from 8 weeks preconception until lactation. Part of the HF mothers received HF diet supplemented with FO (3%, HFFO: 35% lipids) only during pregnancy. FO did not attenuate the increase in weight gain, glycemia, and adiposity induced by maternal HF diet in male (M) and female (F) offspring at weaning. In the soleus muscle, HF-M offspring tended to higher content of triglycerides (P=0.08). HF-F offspring tended to a higher content of monounsaturated fatty acids (P=0.06) and a higher rate of de novo lipogenesis (P=0.01). FO increased the docosahexaenoic acid content in soleus of both sexes (P<0.05). HF-M and -F offspring showed reduced mitochondria density. They exhibited misalignment of sarcomeres, increased damaged mitochondria (P<0.0001), with reduced mitochondrial area (P<0.0001) and perimeter (P<0.0001), attenuated by FO (P<0.05). HF-M exhibited lower protein expression of mitochondrial biogenesis marker PGC1α (P=0.04), mitochondrial transcriptional factor Tfam mRNA (P=0.06), thermogenic/mitochondriogenesis marker Sln (P=0.002), uncoupling protein 3 (UCP3: P=0.059), and antioxidant protein mitochondrial superoxide dismutase (P=0.03) suggesting impaired mitochondriogenesis and increased oxidative stress, mechanisms contributing to reduced mitochondria density and to higher damaged mitochondria. Decreased mitochondrial fission marker (p-DRP1, P=0.02), concomitant with smaller and less circular mitochondria, suggests reduced fission. FO attenuated these changes and, additionally, increased the fusion marker mitofusin-2. Electron transport chain proteins were unaltered in HF offspring of both sexes, however, HFFO-M exhibited increased mitochondrial complexes I (P=0.005) and III (P=0.04). Differently, HF-F exhibited lower protein expression of mitochondrial fusion marker OPA1 (P=0.02 vs C), reversed by FO (P=0.03) accompanied by larger mitochondria, suggesting increased fusion that may contribute to reduced mitochondrial density in HFFO-F (P=0,0002 vs HF). Additionally, FO increased PGC1α (P=0.03) and UCP3 (P=0.06), partially attenuating mitochondria damage. Therefore, maternal FO supplementation during pregnancy partially mitigates sex-specific alterations in skeletal muscle mitochondria induced by maternal HF diet in offspring at weaning, which may have repercussions on offspring phenotype throughout life.