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

Abstract

Animals have adapted behavioral and physiological strategies to conserve energy during periods of adverse conditions. Hepatic glucose is one such adaptation used by grazing animals. While large vertebrates have been shown to have feed utilization and deposition of nutrients—fluctuations in metabolic rate—little is known about the regulating mechanism that controls hepatic metabolism in yaks under grazing conditions in the cold season. Hence, the objective of this research was to integrate transcriptomic and metabolomic data to better understand how the hepatic responds to chronic nutrient stress. Our analyses indicated that the blood parameters related to energy metabolism (glucose, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, lipoprotein lipase, insulin, and insulin-like growth factor 1) were significantly (p < 0.05) lower in the cold season. The RNA-Seq results showed that malnutrition inhibited lipid synthesis (particularly fatty acid, cholesterol, and steroid synthesis), fatty acid oxidation, and lipid catabolism and promoted gluconeogenesis by inhibiting the peroxisome proliferator-activated receptor (PPAR) and PI3K-Akt signaling pathways. For metabolite profiles, 359 metabolites were significantly altered in two groups. Interestingly, the cold season group remarkably decreased glutathione and phosphatidylcholine (18:2 (2E, 4E)/0:0). Moreover, integrative analysis of the transcriptome and metabolome demonstrated that glycolysis or gluconeogenesis, PPAR signaling pathway, fatty acid biosynthesis, steroid biosynthesis, and glutathione metabolism play an important role in the potential relationship between differential expression genes and metabolites. The reduced lipid synthesis, fatty acid oxidation, and fat catabolism facilitated gluconeogenesis by inhibiting the PPAR and PI3K-Akt signaling pathways to maintain the energy homeostasis of the whole body in the yak, thereby coping with the shortage of forages and adapting to the extreme environment of the Qinghai-Tibetan Plateau (QTP).

Lipid Metabolic Disorders Induced by Organophosphate Esters in Silver Carp from the Middle Reaches of the Yangtze River

“…Moreover, the high expression of ppar α could result in a decrease of CHO and TG in hepatocytes by regulating its target genes related to lipid metabolism, including cyp7a1 , ldlr , acsl3 , and so on. − These results suggested that the down-regulation of ppar α induced by OPEs in the present study was probably attributed to the increased TG and CHO in silver carp. Additionally, Acsl catalyzes the synthesis of fatty acyl-CoA thioesters, which are eventually used for the production of membrane lipids, lipid storage as well as fatty acid metabolism. , Current literature demonstrated that the high transcription of Acsl1 could decrease fatty acid β-oxidation and finally led to the increase in the content of TG. , Therefore, the increased mRNA expression of acsl after exposure to OPEs might contribute to the increased TG levels in the serum of silver carp. Changes in the mRNA transcription levels of certain genes related to lipid metabolism induced by the OPEs were also observed in several previous studies.…”

“…53,54 Current literature demonstrated that the high transcription of Acsl1 could decrease fatty acid β-oxidation and finally led to the increase in the content of TG. 55,56 Therefore, the increased mRNA expression of acsl after exposure to OPEs might contribute to the increased TG levels in the serum of silver carp. Changes in the mRNA transcription levels of certain genes related to lipid metabolism induced by the OPEs were also observed in several previous studies.…”

Quantitative Proteomic Analysis of Tibetan Pig Livers at Different Altitudes

“…Previous studies have reported that peroxisome proliferator-activated receptor (PPAR), a steroid hormone receptor, is highly expressed in the liver and regulates intracellular lipid metabolism [ 31 ]. High-altitude animals are able to reduce lipid synthesis by inhibiting the PPAR signaling pathway, thus maintaining the energy homeostasis of the organism [ 32 , 33 ]. Quantitative proteomics showed that the “PPAR signaling pathway” was significantly enriched in three Tibetan pig liver KEGG pathways ( Figure 4 ).…”

Identification of hub biomarkers and exploring the roles of immunity, M6A, ferroptosis, or cuproptosis in rats with diabetic erectile dysfunction

“…PPAR signaling pathway was significantly related to lipid metabolism, adipocyte differentiation, gluconeogenesis, and so forth. 54,55 HIF-1 was a transcriptional activator that mediated cellular adaptation to hypoxia. HIF-1 pathway was involved in anaerobic metabolism and tumor progression, and so forth.…”

“…PPARs had three subtypes (PPARα, PPARβ, and PPARγ). PPAR signaling pathway was significantly related to lipid metabolism, adipocyte differentiation, gluconeogenesis, and so forth 54,55 . HIF‐1 was a transcriptional activator that mediated cellular adaptation to hypoxia.…”