Increasing evidence indicates that lean fish consumption may benefit cardiovascular health. High cholesterol and low n-3 PUFA concentrations in serum are associated with an increased risk of coronary heart disease; therefore, it is of interest to investigate effects of cod intake on cholesterol and n-3 PUFAs in serum and tissues. Hypercholesterolemic obese Zucker fa/fa rats were fed diets containing 25% protein from baked cod fillet and 75% protein from casein (Baked Cod Diet), or casein as the sole protein source (Control Diet) for four weeks. Consuming Baked Cod Diet resulted in lower serum cholesterol and lower hepatic mRNA concentrations of HMG-CoA reductase and sterol O-acyltransferase-2 without affecting serum bile acid concentration, faecal excretion of cholesterol and bile acid, and hepatic concentrations of bile acids, cholesterol and cholesterol 7 alpha-hydroxylase mRNA when compared to Control Diet. Rats fed Baked Cod Diet had higher concentrations of n-3 PUFAs in serum, liver, skeletal muscle and adipose tissue. To conclude, baked cod fillet intake resulted in lower serum cholesterol, which was probably caused by lower endogenous cholesterol synthesis, and higher n-3 PUFA in serum and tissues in obese Zucker fa/fa rats. These findings support the evidence that lean fish consumption might benefit cardiovascular health.

Lipid droplet is a dynamic organelle that undergoes periods of biogenesis and degradation under environmental stimuli. The excessive accumulation of lipid droplets is the major characteristic of non-alcoholic fatty liver disease (NAFLD). Moderate aerobic exercise is a powerful intervention protecting against the progress of NAFLD. However, its impact on lipid droplet dynamics remains ambiguous. Mice were fed with 15 weeks of high-fat diet in order to induce NAFLD. Meanwhile, the mice performed 15 weeks of treadmill exercise. Our results showed that 15 weeks of regular moderate treadmill exercise alleviated obesity, insulin intolerance, hyperlipidemia, and hyperglycemia induced by HFD. Importantly, exercise improved histological phenotypes of NAFLD, including hepatic steatosis, inflammation, and locular ballooning, as well as prevented liver fat deposition and liver injury induced by HFD. Exercise reduced hepatic lipid droplet size, and moreover, it reduced PLIN2 protein level and increased PLIN3 protein level in the liver of HFD mice. Interestingly, our results showed that exercise did not significantly affect the gene expressions of DGAT1, DGAT2, or SEIPIN, which were involved in TG synthesis. However, it did reduce the expressions of FITM2, CIDEA, and FSP27, which were major involved in lipid droplet growth and budding, and lipid droplet expansion. In addition, exercise reduced ATGL protein level in HFD mice, and regulated lipophagy-related markers, including increasing ATG5, LAMP1, LAMP2, LAL, and CTSD, decreasing LC3II/I and p62, and promoting colocalization of LAMP1 with LDs. In summary, our data suggested that 15 weeks of moderate treadmill exercise was beneficial for regulating liver lipid droplet dynamics in HFD mice by inhibiting abnormal lipid droplets expansion and enhancing clearance of lipid droplets by lysosomes during the lipophagic process, which might provide highly flexible turnover for lipid mobilization and metabolism. Abbreviations: β-actin: actin beta; ATG5: autophagy related 5; LAMP2: lysosomal-associated membrane protein 2; LAMP1: lysosomal-associated membrane protein 1; SQSTM1/p62: sequestosome 1; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; ATGL: adipose triglyceride lipase; CSTD: cathepsin D; LAL: lysosomal acid lipase; DGAT1: diacylglycerol-o-acyltransferase 1; DGAT2: diacylglycerol-o-acyltransferase 2; CIDEA: cell death inducing dffa-like effector a; CIDEC/FSP27: cell death inducing dffa-like effector c; FITM2: fat storage-inducing transmembrane protein 2; PLIN2: adipose differentiation related protein; PLN3: tail-interacting protein 47; HSP90: heat shock protein 90; SREBP1c: sterol regulatory element binding protein-1c; chREBP: carbohydrate response element binding protein.