Ivo P van de Peppel, Anuradha Rao, Marleen B Dommerholt, Laura Bongiovanni, Rachel Thomas, Alain de Bruin, Saul J Karpen, Paul A Dawson, Henkjan J Verkade, Johan W Jonker
SCOPE: The apical sodium-dependent bile acid transporter (ASBT, SLC10A2) is important in the enterohepatic cycling of bile acids and thereby in the intestinal absorption of lipids. ASBT inhibition has been shown to improve aspects of the metabolic syndrome, but the underlying mechanisms have remained unclear. Here we investigated the effect of ASBT inhibition on the uptake of specific fatty acids and its consequences for diet-induced obesity and non-alcoholic fatty liver disease (NAFLD)...
October 20, 2020: Molecular Nutrition & Food Research
Soeren Ocvirk, Stephen J D O'Keefe
Colorectal cancer (CRC) risk is predominantly driven by environmental factors, in particular diet. A high intake of dietary fat has been implicated as a risk factor inducing the formation of pre-neoplastic lesions (e.g., adenomatous polyps) and/or exacerbating colonic tumorigenesis. Recent data attributed the tumor-promoting activity of high-fat diets to their effects on gut microbiota composition and metabolism, in particular with regard to bile acids. Bile acids are synthesized in the liver in response to dietary fat and facilitate lipid absorption in the small intestine...
October 15, 2020: Seminars in Cancer Biology
Xuan He, Shannon McClorry, Olle Hernell, Bo Lönnerdal, Carolyn M Slupsky
Lipid digestion is critical for infant development, and yet, the interconnection between lipid digestion and the microbiota is largely understudied. This review focuses on digestion of the human milk fat globule and summarizes the current understanding of the mechanisms underlying this process in infants. We first discuss the partial hydrolysis of milk fat in the stomach, which leads to rearrangement of lipid droplets, creating a lipid-water interface necessary for duodenal lipolysis. In the first few months of life, secretion of pancreatic triglyceride lipase, phospholipase A2 , and bile salts is immature...
August 14, 2020: Nutrition Research
Ping-Ting Xiao, Shi-Yu Liu, Yu-Jia Kuang, Zheng-Meng Jiang, Yang Lin, Zhi-Shen Xie, E-Hu Liu
ETHNOPHARMACOLOGICAL RELEVANCE: Sea buckthorn is popularly used as a herbal medicine and food additive in the world. Sea buckthorn flavonoids (SF) is reported to have an ameliorative effect on obesity and hyperlipidemia (HLP). AIM: To identify the major bioactive compounds and the lipid-lowering mechanism of SF. METHODS: We used network pharmacology analysis and in vitro experiments to identify the major bioactive compounds and the lipid-lowering mechanism of SF...
September 9, 2020: Journal of Ethnopharmacology
Yunxia Yang, Jianfa Zhang
Circadian rhythms are biological systems that synchronize cellular circadian oscillators with the organism's daily feeding-fasting or rest-activity cycles in mammals. Circadian rhythms regulate nutrient absorption and utilization at the cellular level, and are closely related to obesity and metabolic disorders. Bile acids are important modulators that facilitate nutrient absorption and regulate energy metabolism. Here, we provide an overview of the current connections and future perspectives between the circadian clock and bile acids metabolism as well as related metabolic diseases...
September 9, 2020: American Journal of Physiology. Gastrointestinal and Liver Physiology
Guang Wang, Bing Wu, Yang Cui, Bo Zhang, Chunyan Jiang, Heyuan Wang
Bile acids (BAs) play essential physiological roles not only by facilitating the absorption and transport of nutrients but also by acting as a complex molecular signaling system. Reduced levels of BAs have been observed in obesity and other metabolic disorders. In the present study, we explored the effect of the dipeptidyl peptidase-4 (DPP-4) inhibitor teneligliptin on BA synthesis, both in vitro and in vivo . In our in vivo experiments, we found that teneligliptin increased the liver, ileal, and serum BA concentrations in mice undergoing teneligliptin treatment for 10 weeks...
July 22, 2020: Chemical Research in Toxicology
Shota Hori, Takayuki Abe, Dong Geun Lee, Satoru Fukiya, Atsushi Yokota, Nao Aso, Bungo Shirouchi, Masao Sato, Satoshi Ishizuka
High-fat (HF) diet induces hepatic steatosis that is a risk factor for noncommunicable diseases such as obesity, type 2 diabetes and cardiovascular disease. Previously, we found that HF feeding in rats increases the excretion of fecal bile acids (BAs), specifically 12α-hydroxylated (12αOH) BAs. Although the liver is the metabolic center in our body, the association between hepatic steatosis and 12αOH BAs in HF-fed rats is unclear. Thus, we investigated extensively BA composition in HF-fed rats and evaluated the association between hepatic steatosis and 12αOH BAs...
May 20, 2020: Journal of Nutritional Biochemistry
Rima H Mistry, Fan Liu, Klaudyna Borewicz, Mirjam A M Lohuis, Hauke Smidt, Henkjan J Verkade, Uwe J F Tietge
SCOPE: The gut microbiota might be a critical modifier of metabolic disease development. Dietary fibers such as galacto-oligosaccharides (GOS) presumably stimulate the growth of bacteria beneficial for metabolic health. This study aimed to assess the impact of GOS on obesity, glucose and lipid metabolism. METHODS & RESULTS: Following Western-type diet feeding (C57BL/6 mice) with or without β-GOS (7% w/w, 15 weeks), body composition, glucose and insulin tolerance tests, lipid profiles, fat kinetics studies and microbiota analyses were performed...
May 7, 2020: Molecular Nutrition & Food Research
Pei Shan Lim, Chui Fung Loke, Yin Wan Ho, Tan Hui Yin
AIMS: To determine the mechanism underlying the serum cholesterol reduction effect by probiotics isolated from local fermented tapioca (Tapai). METHODS AND RESULTS: Lactic acid bacteria strains were isolated and examined for acid tolerance, bile salt resistance and hypocholesterolemic properties. Among the isolates, Lact. plantarum TAR4 showed the highest cholesterol reduction ability (48.01%). The focus in the in vivo trial was to elucidate the cholesterol balance from findings pertaining to serum cholesterol reduction in rat model fed with high fat diet via oral administration...
April 30, 2020: Journal of Applied Microbiology
Li-Min Liang, Jun-Jie Zhou, Feng Xu, Pei-Hua Liu, Lan Qin, Li Liu, Xiao-Dong Liu
Peptide transporter 1 (PepT1), highly expressed on the apical membrane of enterocytes, is involved in energy balance and mediates intestinal absorption of peptidomimetic drugs. In this study, we investigated whether and how diabetes affected the function and expression of intestinal PepT1. Diabetes was induced in rats by combination of high-fat diet and low dose streptozocin injection. Pharmacokinetics study demonstrated that diabetes significantly decreased plasma exposures of cephalexin and acyclovir following oral administration of cephalexin and valacyclovir, respectively...
April 27, 2020: Acta Pharmacologica Sinica
Anuradha Rao, Ivo P van de Peppel, Sanjeev Gumber, Saul J Karpen, Paul A Dawson
Non-alcoholic fatty liver disease (NAFLD) is a major growing worldwide health problem. We previously reported that interruption of the enterohepatic circulation of bile acids using a non-absorbable apical sodium-dependent bile acid transporter inhibitor (ASBTi; SC-435) reduced the development of NAFLD in high fat diet fed mice. However, the ability of ASBTi treatment to impact the progression of NAFLD to non-alcoholic steatohepatitis (NASH) and fibrosis in a diet-induced mouse model remains untested. In the current study, we assessed whether ASBTi treatment is hepatoprotective in the choline-deficient, L-amino acid-defined (CDAA) diet model of NASH-induced fibrosis...
2020: Frontiers in Medicine
Sei Higuchi, Tiara R Ahmad, Donovan A Argueta, Pedro A Perez, Chen Zhao, Gary J Schwartz, Nicholas V DiPatrizio, Rebecca A Haeusler
OBJECTIVES: Lipid mediators in the GI tract regulate satiation and satiety. Bile acids (BAs) regulate the absorption and metabolism of dietary lipid in the intestine, but their effects on lipid-regulated satiation and satiety are completely unknown. Investigating this is challenging because introducing excessive BAs or eliminating BAs strongly impacts GI functions. We used a mouse model (Cyp8b1-/- mice) with normal total BA levels, but alterations in the composition of the BA pool that impact multiple aspects of intestinal lipid metabolism...
February 28, 2020: Gut
Vik Meadows, Lindsey Kennedy, Debjyoti Kundu, Gianfranco Alpini, Heather Francis
In the past ten years, our understanding of the importance of bile acids has expanded from fat absorption and glucose/lipid/energy homeostasis into potential therapeutic targets for amelioration of chronic cholestatic liver diseases. The discovery of important bile acid signaling mechanisms, as well as their role in metabolism, has increased the interest in bile acid/bile acid receptor research development. Bile acid levels and speciation are dysregulated during liver injury/damage resulting in cytotoxicity, inflammation, and fibrosis...
2020: Frontiers in Medicine
Bin Xia, Ping Lin, Yubin Ji, Jiayu Yin, Jin Wang, Xiaoqian Yang, Ting Li, Zixun Yang, Fahui Li, Shoudong Guo
BACKGROUND: The LDL-C lowering effect of ezetimibe has been attributed primarily to increased catabolism of LDL-C via up-regulation of LDL receptor (LDLR) and decreased cholesterol absorption. Recently, ezetimibe has been demonstrated to have reverse cholesterol transport (RCT) promoting effects in mice, hamsters and humans. However, the underlying mechanisms are still not clear. The aim of this study is to investigate whether ezetimibe improves RCT-related protein expression in LDLR-/- hamsters...
February 8, 2020: Lipids in Health and Disease
Sarah Farr, Bogdan Stankovic, Simon Hoffman, Hassan Masoudpoor, Chris Baker, Jennifer Taher, Angela E Dean, Sayeepriyadarshini Anakk, Khosrow Adeli
Postprandial dyslipidemia is a common feature of insulin-resistant states and contributes to increased cardiovascular disease risk. Recently, bile acids have been recognized beyond their emulsification properties as important signaling molecules that promote energy expenditure, improve insulin sensitivity, and lower fasting lipemia. Although bile acid receptors have become novel pharmaceutical targets, their effects on postprandial lipid metabolism remain unclear. Here, we investigated the potential role of bile acids in regulation of postprandial chylomicron production and triglyceride excursion...
April 1, 2020: American Journal of Physiology. Gastrointestinal and Liver Physiology
Olivia Pabois, Amandine Antoine-Michard, Xi Zhao, Jasmin Omar, Faizah Ahmed, Florian Alexis, Richard D Harvey, Isabelle Grillo, Yuri Gerelli, Myriam M-L Grundy, Balazs Bajka, Peter J Wilde, Cécile A Dreiss
Methylcellulose (MC) has a demonstrated capacity to reduce fat absorption, hypothetically through bile salt (BS) activity inhibition. We investigated MC cholesterol-lowering mechanism, and compared the influence of two BS, sodium taurocholate (NaTC) and sodium taurodeoxycholate (NaTDC), which differ slightly by their architecture and exhibit contrasting functions during lipolysis. BS/MC bulk interactions were investigated by rheology, and BS behaviour at the MC/water interface studied with surface pressure and ellipsometry measurements...
March 1, 2020: Carbohydrate Polymers
Xinyang Song, Ximei Sun, Sungwhan F Oh, Meng Wu, Yanbo Zhang, Wen Zheng, Naama Geva-Zatorsky, Ray Jupp, Diane Mathis, Christophe Benoist, Dennis L Kasper
The metabolic pathways encoded by the human gut microbiome constantly interact with host gene products through numerous bioactive molecules1 . Primary bile acids (BAs) are synthesized within hepatocytes and released into the duodenum to facilitate absorption of lipids or fat-soluble vitamins2 . Some BAs (approximately 5%) escape into the colon, where gut commensal bacteria convert them into various intestinal BAs2 that are important hormones that regulate host cholesterol metabolism and energy balance via several nuclear receptors and/or G-protein-coupled receptors3,4 ...
December 25, 2019: Nature
Tao Han, Yangge Lv, Shijia Wang, Tao Hu, Hao Hong, Zan Fu
BACKGROUND: The cholesterol gallstones diseases (CGD) is highly correlated with metabolic syndrome and type 2 diabetes. The present study aimed to investigate preventive effects of pioglitazone (PIO), an antidiabetic drug, on the CGD in guinea pigs fed with a lithogenic diet (LD). METHODS: The guinea pigs were fed with the LD for 8 weeks. All guinea pigs were grouped as follows: low fat diet; LD; LD plus PIO (4 mg/kg); LD plus PIO (8 mg/kg); LD plus ezetimibe (EZE) (2 mg/kg)...
December 11, 2019: Lipids in Health and Disease
Victoria Higgins, Shervin Asgari, Jill K Hamilton, Anna Wolska, Alan T Remaley, Bolette Hartmann, Jens J Holst, Khosrow Adeli
BACKGROUND: With increased rates of obesity and insulin resistance in youth, development of postprandial dyslipidemia, an important cardiovascular disease risk factor, is a concern. Glucagon-like peptides (i.e. GLP-1 and GLP-2) and bile acids have been shown to regulate dietary fat absorption and postprandial lipids in animal models and humans. We hypothesize that the physiological response of GLPs and bile acids to dietary fat ingestion is impaired in adolescents with obesity and this associates with marked postprandial dyslipidemia and insulin resistance...
December 11, 2019: Journal of Clinical Endocrinology and Metabolism
Michael K Badman, Jin Chen, Sachin Desai, Soniya Vaidya, Srikanth Neelakantham, Jie Zhang, Lu Gan, Kate Danis, Bryan Laffitte, Lloyd B Klickstein
Tropifexor (LJN452) is a potent, orally available, non-bile acid farnesoid X receptor agonist under clinical development for chronic liver diseases. Here, we present results from a first-in-human study of tropifexor following single- and multiple-ascending doses (SAD/MAD) and food effect substudy in healthy volunteers. The SAD study included 6 fasted cohorts receiving 10- to 3000-µg tropifexor or placebo and 1 cohort receiving 300-µg tropifexor with a high-fat meal. The MAD study included 4 lean cohorts receiving 10 to 100 µg and 1 obese cohort receiving 30-µg once-daily doses or placebo for 14 days...
December 10, 2019: Clinical Pharmacology in Drug Development
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