A cottonseed oil-enriched diet improves liver and plasma lipid levels in a male mouse model of fatty liver

Submitted to: American Journal of Physiology - Regulatory Integrative & Comparative Physiology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/2/2022
Publication Date: 12/12/2022
Citation: Son, Y., Shockey, J., Dowd, M.K., Shieh, J.G., Cooper, J.A., Paton, C.M. 2023. A cottonseed oil-enriched diet improves liver and plasma lipid levels in a male mouse model of fatty liver. American Journal of Physiology - Regulatory Integrative & Comparative Physiology. 324: R171–R182 https://doi.org/10.1152/ajpregu.00052.2022.
DOI: https://doi.org/10.1152/ajpregu.00052.2022

Interpretive Summary: Cardiovascular disease is the primary cause of death in the developed world. High blood lipid levels is one of the most significant risk factors contributing to cardiovascular disease. The liver is a primary site of production of plasma lipids, making it a major target for lipid-lowering therapies. Statins are the most effective treatment for reducing lipid-mediated cardiovascular disease risk, but despite their effectiveness, statins can result in serious side effects. For this reason, there is a growing interest in natural methods for lowering blood plasma lipid levels. Previous studies have shown that a diet rich in cottonseed oil lowers lipid levels in animals as well as humans. Previous work has found that the lipid-lowering effects of cottonseed oil is caused by the combination of dihydrosterculic acid (DHSA) and polyunsaturated fatty acid content. Previous research on cottonseed oil-enriched diets has been mostly conducted in healthy animals or humans where it consistently shows improvements in plasma lipid levels, here we present the results observed when cottonseed oil diets are instead used to try to remedy pre-existing negative health markers in obese mice previously fed a high-fat diet prior to be switched to medium-calorie level cottonseed oil diets.

Technical Abstract: A high-fat (HF) diet causes fatty liver, hyperlipidemia, and hypercholesterolemia, and cottonseed oil (CSO) has been shown to improve liver and plasma lipids in human and mouse models. The purpose of this study was to determine the effect of CSO versus olive oil (OO)-enriched diets on lipid levels in a HF diet model of fatty liver disease. We placed mice on a HF diet to induce obesity and fatty liver, after which mice were placed on CSO or OO diets, with chow and HF (5.1 Kcal/g) groups as control. When CSO and OO-fed mice were given isocaloric diets with the HF group, there were no differences in body weight, plasma, or hepatic lipids. However, when the CSO and OO diets were reduced in calories (4.0 Kcal/g), CSO and OO groups reduced body weight. The CSO group had lower plasma total cholesterol (-56%±6, p<0.01), free cholesterol (-53%±7, p<0.01), triglycerides (-61%±14, p<0.01), and LDL (-42%±16, p=0.01) vs. HF group whereas the OO diet lowered LDL (-18%±12, p=0.05) vs. HF. Furthermore, the CSO diet decreased hepatic total cholesterol (-40%±12, p<0.01), free cholesterol (-23%±11, p=0.04), and triglycerides (-47%±12, p=0.02). There were no significant changes in lipogenesis and fatty acid oxidation among groups. However, the CSO group increased lipid oxidative gene expression in liver and dihydrosterculic acid increased PPARa target genes with in vitro models. Taken together, consuming a reduced calorie diet enriched in CSO reduces liver and plasma lipid profiles in an obese model of fatty liver.