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A chronic high-fat diet (HFD) produces obesity, leading to pathological consequences in the liver and skeletal muscle. The fat in the liver leads to accumulation of a large number of intrahepatic lipid droplets (LD), which are susceptible to oxidation. Obesity also affects skeletal muscle, increasing LD and producing insulin signaling impairment. Physalis peruviana L. (PP) (Solanaceae) is rich in peruvioses and has high antioxidant activity. We assessed the ability of PP to enhance insulin-dependent glucose uptake in skeletal muscle and the capacity to prevent both inflammation and lipoperoxidation in the liver of diet-induced obese mice. Male C57BL/6J mice were divided into groups and fed for eight weeks: control diet (C; 10% fat, 20% protein, 70% carbohydrates); C + PP (300 mg/kg/day); HFD (60% fat, 20% protein, 20% carbohydrates); and HFD + PP. Results suggest that PP reduces the intracellular lipoperoxidation level and the size of LD in both isolated hepatocytes and skeletal muscle fibers. PP also promotes insulin-dependent skeletal muscle glucose uptake. In conclusion, daily consumption of 300 mg/kg of fresh pulp of PP could be a novel strategy to prevent the hepatic lipoperoxidation and insulin resistance induced by obesity.

Dietary intake of eicosapentaenoic/docosahexaenoic acid (EPA/DHA) reduces insulin resistance and hepatic manifestations through the regulation of metabolism in the liver. Obese mice present insulin resistance and lipid accumulation in intracellular lipid droplets (LDs). LD-associated proteins perilipin (Plin) have an essential role in both adipogenesis and lipolysis; Plin5 regulates lipolysis and thus contributes to fat oxidation. The purpose of this study was to compare the effects of deodorized refined salmon oil (DSO) and its polyunsaturated fatty acids concentrate (CPUFA) containing EPA and DHA, obtained by complexing with urea, on obesity-induced metabolic alteration. CPUFA maximum content was determined using the Box–Behnken experimental design based on Surface Response Methodology. The optimized CPUFA was administered to high-fat diet (HFD)-fed mice (200 mg/kg/day of EPA + DHA) for 8 weeks. No significant differences (p > 0.05) in cholesterol, glycemia, LDs or transaminase content were found. Fasting insulin and hepatic Plin5 protein level increased in the group supplemented with the EPA + DHA optimized product (38.35 g/100 g total fatty acids) compared to obese mice without fish oil supplementation. The results suggest that processing salmon oil by urea concentration can generate an EPA+DHA dose useful to prevent the increase of fasting insulin and the decrease of Plin5 in the liver of insulin-resistant mice.

Chronic high-fat diet feeding is associated with obesity and accumulation of fat in the liver, leading to the development of insulin resistance and non-alcoholic fatty liver disease. This condition is characterized by the presence of a high number of intrahepatic lipid droplets (LD), with changes in the perilipin pattern covering them. This work aimed to describe the distribution of perilipin 2 (Plin2), a LD-associated protein involved in neutral lipid storage, and perilipin 5 (Plin5), that is favoring the lipid oxidation in LD, and to evaluate lipid peroxidation through live-cell visualization using the lipophilic fluorescent probe C11-BODIPY581/591 in fresh hepatocytes isolated from high-fat diet (HFD)-fed mice. Male C57BL/6J adult mice were divided into control and HFD groups and fed with a control diet (Control; 10% fat, 20% protein, and 70% carbohydrates) or a HFD (60% fat, 20% protein, and 20% carbohydrates) for 8 weeks. The animals fed the HFD show a significant increase of Plin2 in LD of hepatocytes. LD from HFD-fed mice have a stronger lipid peroxidation level than control hepatocytes. These data provide evidence that obesity status is accompanied by a higher degree of lipid peroxidation in hepatocytes, both in the cytoplasm and in the fats stored inside the LD. Novelty bullets • Our study shows that lipid droplets from isolated hepatocytes in HFD-fed mice have a stronger lipid peroxidation level than control hepatocytes. • C11-BODIPY581/591 is a useful tool to measure the initial level of intracellular lipid peroxidation in single isolated hepatocytes. • Perilipins pattern changes with HFD feeding, showing an increase of Plin2 covering lipid droplets.