Sex Differences in Fish Oil and Olanzapine Effects on Gut Microbiota in Diet-Induced Obese Mice

Children are prescribed second-generation antipsychotic (SGA) medications, such as olanzapine (OLZ) for FDA-approved and “off-label” indications. The long-term impact of early-life SGA medication exposure is unclear. Olanzapine and other SGA medications are known to cause excessive weight gain in young and adult patients, suggesting the possibility of long-term complications associated with the use of these drugs, such as obesity, diabetes, and heart disease. Further, the weight gain effects of OLZ have previously been shown to depend on the presence of gut bacteria and treatment with OLZ, which shifts gut bacteria toward an “obesogenic” profile. The purpose of the current study was to evaluate changes in gut bacteria in adult mice following early life treatment with OLZ and being fed either a high-fat diet or a high-fat diet supplemented with fish oil, which has previously been shown to counteract gut dysbiosis, weight gain, and inflammation produced by a high-fat diet. Female and male C57Bl/6J mice were fed a high fat diet without (HF) or with the supplementation of fish oil (HF-FO) and treated with OLZ from postnatal day (PND) 37–65 resulting in four groups of mice: mice fed a HF diet and treated with OLZ (HF-OLZ), mice fed a HF diet and treated with vehicle (HF), mice fed a HF-FO diet and treated with OLZ (HF-FO-OLZ), and mice fed a HF-FO diet and treated with vehicle (HF-FO). Following euthanasia at approximately 164 days of age, we determined changes in gut bacteria populations and serum LPS binding protein, an established marker of gut inflammation and dysbiosis. Our results showed that male HF-FO and HF-FO-OLZ mice had lower body weights, at sacrifice, compared to the HF group, with a comparable body weight across groups in female mice. HF-FO and HF-FO-OLZ male groups also exhibited lower serum LPS binding protein levels compared to the HF group, with no differences across groups in female mice. Gut microbiota profiles were also different among the four groups; the Bacteroidetes-to-Firmicutes (B/F) ratio had the lowest value of 0.51 in the HF group compared to 0.6 in HF-OLZ, 0.9 in HF-FO, and 1.1 in HF-FO-OLZ, with no differences in female mice. In conclusion, FO reduced dietary obesity and its associated inflammation and increased the B/F ratio in male mice but did not benefit the female mice. Although the weight lowering effects of OLZ were unexpected, FO effects persisted in the presence of olanzapine, demonstrating its potential protective effects in male subjects using antipsychotic drugs.

The Effects of Fish Oil on Cardiovascular Diseases: Systematical Evaluation and Recent Advance

Fish oil is rich in unsaturated fatty acids, i.e., eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), both of which are widely distributed in the body such as heart and brain. In vivo and in vitro experiments showed that unsaturated fatty acids may have effects of anti-inflammation, anti-oxidation, protecting vascular endothelial cells, thrombosis inhibition, modifying autonomic nerve function, improving left ventricular remodeling, and regulating blood lipid. Given the relevance to public health, there has been increasing interest in the research of potential cardioprotective effects of fish oil. Accumulated evidence showed that fish oil supplementation may reduce the risk of cardiovascular events, and, in specific, it may have potential benefits in improving the prognosis of patients with hypertension, coronary heart disease, cardiac arrhythmias, or heart failure; however, some studies yielded inconsistent results. In this article, we performed an updated systematical review in order to provide a contemporary understanding with regard to the effects of fish oil on cardiovascular diseases.

Different Fish Meal and Fish Oil Dietary Levels in European Sea Bass: Welfare Implications After Acute Confinement Stress

To provide practical feeding management guidelines preceding a stressful episode during farming practices, European sea bass juveniles (initial weight: 72.3 g) were fed for 60-days different fish meal (FM) and fish oil (FO) dietary levels [high (30% FM, 15% FO, FM30/FO15), intermediate (20% FM, 7% FO, FM20/FO7), and low (10% FM, 3% FO, FM10/FO3)] in triplicate conditions. Fish were then fasted for 36 h and exposed to a 2-h acute crowding (80 kg m–3 biomass). Plasma biochemistry, skin mucus parameters and gene expression of stress and immune-related genes were performed before, at 2 and 24 h after crowding. At the end of the trial, the FM10/FO3 group showed lower final body weight, weight gain, and specific growth rate compared to the other treatments. Most of the plasma parameters were mainly affected by crowding condition rather than diet; however, after stress, lactate was higher in the FM30/FO15 group compared to the other treatments. Similarly, protease, antiprotease, peroxidase and lysozyme in skin mucus were mostly affected by crowding conditions, while fish fed FM10/FO3 displayed higher skin mucosal IgM and bactericidal activity against Vibrio anguillarum and V. harveyi. Most of the stress-related genes considered (hsp70 and gr-1 in the brain; hsp70, gr-1 and gr-2 in the head kidney), showed an overall expression pattern that increased over time after stress, in addition, hsp70 in the head kidney was also up-regulated in fish fed FM30/FO15 after stress. Higher plasmatic lactate together with the up-regulation of some stress-related transcripts suggest a higher reactivity to acute crowding of the stress-response mechanism in fish fed high FM and FO dietary levels. Otherwise, the higher skin mucosal IgM and bactericidal activity observed in fish fed FM10/FO3 dietary levels seems to indicate that acute crowding was able to activate a higher pro-inflammatory response in this treatment. Overall, the results of the present study seem to indicate that 10% FM and 3% FO dietary levels might affect stress and immune responses.