Project description:The ketogenic diet has been successful in promoting weight loss among patients that have struggled with weight gain. This is due to the cellular switch in metabolism that utilizes liver-derived ketone bodies for the primary energy source rather than glucose. Fatty acid transport protein 2 (FATP2) is highly expressed in liver, small intestine, and kidney where it functions in both the transport of exogenous long chain fatty acids (LCFA) and in the activation to CoA thioesters of very long chain fatty acids (VLCFA). We have completed a multi-omic study of FATP2-null (Fatp2-/-) mice maintained on a ketogenic diet (KD) or paired control diet (CD), with and without a 24-hour fast (KD-fasted and CD-fasted) to address the impact of deleting FATP2 under high-stress conditions. Control (wt/wt) and Fatp2-/- mice were maintained on their respective diets for 4-weeks. Afterwards, half the population was sacrificed while the remaining were fasted for 24-hours prior to sacrifice. We then performed paired-end RNA-sequencing on the whole liver tissue to investigate differential gene expression. The differentially expressed genes mapped to ontologies such as the metabolism of amino acids and derivatives, fatty acid metabolism, protein localization, and components of the immune system’s complement cascade, and were supported by the proteome and histological staining.
Project description:Fatty acid transport protein 2 (FATP2) is highly expressed in liver, small intestine, and kidney where it functions in both the uptake of exogenous long chain fatty acids (LCFAs) and in the activation to CoA thioesters of very long chain fatty acids (VLCFAs). Here we address the phenotypic impacts of deleting FATP2 followed by an unbiased RNA-seq analysis of the liver transcriptome. Wild type (C57BL/6J) and fatp2 null (fatp2-/-) mice (5 weeks old) were maintained on a standard chow diet for 6 weeks (11 weeks old). The male fatp2-/- mice had 258 differentially expressed genes (DEGs) and the female mice had a total of 91. Of significance was the finding that most of the genes with increased expression in the fatp2-/- liver are regulated by the transcription factor peroxisome proliferator-activated receptor alpha (PPARα). Taken together, FATP2 has a broad impact on the expression of key lipid metabolic genes in the liver regulated by PPARα.
Project description:Acetaminophen is a widely used antipyretic and analgesic drug, and its overdose is the leading cause of drug-induced acute liver failure. This study aimed to investigate the effect and mechanism of Lacticaseibacillus casei Shirota (LcS), an extensively used and highly studied probiotic, on acetaminophen-induced acute liver injury. C57BL/6 mice were gavaged with LcS suspension or saline once daily for 7 days before the acute liver injury was induced via intraperitoneal injection of 300 mg/kg acetaminophen. The results showed that LcS significantly decreased acetaminophen-induced liver and ileum injury, as demonstrated by reductions in the increases in aspartate aminotransferase, total bile acids, total bilirubin, indirect bilirubin and hepatic cell necrosis. Moreover, LcS alleviated the acetaminophen-induced intestinal mucosal permeability, elevation in serum IL-1α and lipopolysaccharide, and decreased levels of serum eosinophil chemokine (eotaxin) and hepatic glutathione levels. Furthermore, analysis of the gut microbiota and metabolome showed that LcS reduced the acetaminophen-enriched levels of Cyanobacteria, Oxyphotobacteria, long-chain fatty acids, cholesterol and sugars in the gut. Additionally, the transcriptome and proteomics showed that LcS mitigated the downregulation of metabolism and immune pathways as well as glutathione formation during acetaminophen-induced acute liver injury. This is the first study showing that pretreatment with LcS alleviates acetaminophen-enriched acute liver injury, and it provides a reference for the application of LcS.
Project description:Intervention group:High flavonoid content fruit and vegetable diet guidance;Control group:No
Primary outcome(s): Flavonoid markers;Salivary cortisol;Blood cortisol;Gut microbiota;Mental Health Assessment Questionnaire;Fecal short chain fatty acids;Changes in defecation habits and traits
Study Design: Parallel
Project description:Insulin secretion by pancreatic b-cells is primarily regulated by glucose; however, hormones and additional nutrients, such as long-chain fatty acids, also play an important role in adjusting insulin output to physiologic needs. We examined the role of the short chain fatty acid receptor, GPR41, in funcion of pancreatic beta cells. GPR41 was specifically over-expressed in beta cells by using rat insulin promoter II (41 Tg).
Project description:This transcriptomic study investigates the effect of therapeutic short-chain fatty acids (SCFA) administration on post-stroke recovery.
2020-01-01 | GSE131788 | GEO
Project description:Short-Chain Fatty Acids Modulate Microbiota Composition and Functional Potential