Gestational fish oil supplementation in a maternal high-fat diet reduces mitochondrial ultrastructural damage and increases fusion proteins in the soleus muscles of weanling rat offspring

Perinatal maternal high-fat (HF) diet induces metabolic disorders in offspring associated with mitochondrial damage in their skeletal muscle. We hypothesized that gestational supplementation with fish oil (FO), rich in n-3 polyunsaturated fatty acids, may attenuate mitochondrial injury in the soleus muscle of male and female weanling HF offspring. Female rats received control or HF diet from 8 weeks premating throughout lactation. During gestation, part of HF dams received HF diet containing 3 % FO. Gestational FO mitigated HF-induced soleus sarcomere misalignment and mitochondrial ultrastructural injury in weanling offspring. FO increased mitochondrial complex proteins I and III in males and uncoupling protein-3 and PGC1α (biogenesis marker) in both sexes. FO enhanced fusion proteins mitofusin-2 (males) and OPA-1 (females) and mitochondrial size, suggesting increased mitochondrial fusion. Thus, gestational FO supplementation to maternal HF diet enhances biogenesis and mitochondrial fusion markers, improving mitochondria quality and potentially function in soleus muscle of weanling HF offspring

IMPACT OF EXPERIMENTAL OBESITY ON DIAPHRAGM STRUCTURE, FUNCTION, AND BIOENERGETICS

Obesity is associated with bioenergetic dysfunction of peripheral muscles; however, little is known regarding the impact of obesity on the diaphragm. We hypothesized that obesity would be associated with diaphragm dysfunction attributable to mitochondrial oxygen consumption and structural and ultrastructural changes. Wistar rat litters were culled to 3 pups to induce early postnatal overfeeding and consequent obesity. Control animals were obtained from unculled litters. From postnatal day 150, diaphragm ultrasonography, computed tomography, high-resolution respirometry, immunohistochemical, biomolecular and ultrastructural histological analyses were performed. The diaphragms of obese animals, compared to those of controls, exhibited presented changes in morphology as increased thickening fraction, diaphragm excursion and diaphragm dome height, as well as increased mitochondrial respiratory capacity coupled to ATP synthesis and maximal respiratory capacity. Fatty acid synthase expression was also higher in obese animals, suggesting a source of energy for the respiratory chain. Myosin heavy chain-IIA was increased, indicating shift from glycolytic toward oxidative muscle fiber profile. Diaphragm tissue also exhibited ultrastructural changes, such as compact, round, and swollen mitochondria with fainter cristae and more lysosomal bodies. Dynamin-1 expression in the diaphragm was reduced in obese rats, suggesting decreased mitochondrial fission. Furthermore, gene expressions of peroxisome gamma proliferator-activated receptor co-activator-1\u3b1 and superoxide dismutase-2 were lower in obese animals than in controls, which may indicate a predisposition to oxidative injury. In conclusion, in the obesity model used herein, muscle fiber phenotype was altered in a manner likely associated with increased mitochondrial respiratory capability, suggesting respiratory adaptation to increased metabolic demand