3′quant mRNA-Seq of Porcine Liver Reveals Alterations in UPR, Acute Phase Response, and Cholesterol and Bile Acid Metabolism in Response to Different Dietary Fats

Abstract

Animal fats are considered to be unhealthy, in contrast to vegetable fats, which are rich in unsaturated fatty acids. However, the use of some fats, such as coconut oil, is still controversial. In our experiment, we divided experimental animals (domestic pigs) into three groups differing only in the type of fat used in the diet: group R: rapeseed oil (n = 5); group B: beef tallow (n = 5); group C: coconut oil (n = 6). After transcriptomic analysis of liver samples, we identified 188, 93, and 53 DEGs (differentially expressed genes) in R vs. B, R vs. C, and B vs. C comparisons, respectively. Next, we performed a functional analysis of identified DEGs with String and IPA software. We observed the enrichment of genes engaged in the unfolded protein response (UPR) and the acute phase response among genes upregulated in B compared to R. In contrast, cholesterol biosynthesis and cholesterol efflux enrichments were observed among genes downregulated in B when compared to R. Moreover, activation of the UPR and inhibition of the sirtuin signaling pathway were noted in C when compared to R. The most striking difference in liver transcriptomic response between C and B was the activation of the acute phase response and inhibition of bile acid synthesis in the latest group. Our results suggest that excessive consumption of animal fats leads to the activation of a cascade of mutually propelling processes harmful to the liver: inflammation, UPR, and imbalances in the biosynthesis of cholesterol and bile acids via altered organelle membrane composition. Nevertheless, these studies should be extended with analysis at the level of proteins and their function.

Integrated Omics analysis of pig muscle metabolism under the effects of dietary Chlorella vulgaris and exogenous enzymes

“…Regarding Control vs CV + R, the SIRT3 and ACOT8 genes, involved in superoxide dismutase activity and peroxisomal lipid metabolism, respectively, are upregulated in the CV + R group. SIRT3 gene encodes a member of the sirtuin family of class III NAD + -dependent histone deacetylases 46 . This enzyme is localised primarily in mitochondria and has been shown to deacetylate and thereby regulate several mitochondrial targets, including acetyl-CoA synthase 2 and glutamate dehydrogenase.…”

Transcriptomic and Metabolomic Analyses Reveal Inhibition of Hepatic Adipogenesis and Fat Catabolism in Yak for Adaptation to Forage Shortage During Cold Season

“…Cholesterol homeostasis in the liver of mammals is maintained through exogenous absorption, endogenous synthesis, and excretion or conversion of cholesterol into bile acids. A reciprocal relationship between these processes regulates circulating cholesterol levels in response to dietary interventions ( Liu et al, 2017 ; Oczkowicz et al, 2020 ). Bile acid, a steroid acid synthesized in the liver, is responsible for fat metabolisms, such as digestion and absorption ( Li R. et al, 2020 ).…”

Consumption of Saturated Fatty Acids‐Rich Lard Benefits Recovery of Experimental Arthritis by Activating PPAR‐γ

“…[16][17][18] But in fact, many USF are universally distributed, and can even be found in animal tallow, which is traditionally defined as unhealthy fat. [19] Chinese population consumes substantial amounts of pork, but it is interesting to observe that RA incidence here is low (about 0.5%). [20] Epidemiology survey rebut the hypothesis that people in northern China who eat more lard are more likely to develop RA.…”

“…[ 16–18 ] But in fact, many USF are universally distributed, and can even be found in animal tallow, which is traditionally defined as unhealthy fat. [ 19 ]…”