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liver fat content and insulin resistance

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https://www.readbyqxmd.com/read/28202906/bar502-a-dual-fxr-and-gpbar1-agonist-promotes-browning-of-white-adipose-tissue-and-reverses-liver-steatosis-and-fibrosis
#1
Adriana Carino, Sabrina Cipriani, Silvia Marchianò, Michele Biagioli, Chiara Santorelli, Annibale Donini, Angela Zampella, Maria Chiara Monti, Stefano Fiorucci
Non-alcoholic steatohepatitis (NASH) is a highly prevalent chronic liver disease. Here, we have investigated whether BAR502, a non-bile acid, steroidal dual ligand for FXR and GPBAR1, reverses steato-hepatitis in mice fed a high fat diet (HFD) and fructose. After 9 week, mice on HFD gained ≈30% of b.w (P < 0.01 versus naïve) and were insulin resistant. These overweighting and insulin resistant mice were randomized to receive HFD or HFD in combination with BAR502. After 18 weeks, HFD mice developed NASH like features with severe steato-hepatitis and fibrosis, increased hepatic content of triacylglycerol and cholesterol and expression of SREPB1c, FAS, ApoC2, PPARα and γ, α-SMA, α1 collagen and MCP1 mRNAs...
February 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28197827/phloretin-prevents-high-fat-diet-induced-obesity-and-improves-metabolic-homeostasis
#2
Sary Alsanea, Mingming Gao, Dexi Liu
Reactive oxygen species generated as a by-product in metabolism play a central role in the development of obesity and obesity-related metabolic complications. The objective of the current study is to explore the possibility to block obesity and improve metabolic homeostasis via phloretin, a natural antioxidant product from apple tree leaves and Manchurian apricot. Both preventive and therapeutic activities of phloretin were assessed using a high-fat diet-induced obesity mouse model. Phloretin was injected intraperitoneally twice weekly into regular and obese mice fed a high-fat diet...
February 14, 2017: AAPS Journal
https://www.readbyqxmd.com/read/28163820/apolipoprotein-ciii-overexpression-induced-hypertriglyceridemia-increases-nonalcoholic-fatty-liver-disease-in-association-with-inflammation-and-cell-death
#3
Adriene A Paiva, Helena F Raposo, Amarylis C B A Wanschel, Tarlliza R Nardelli, Helena C F Oliveira
Nonalcoholic fatty liver disease (NAFLD) is the principal manifestation of liver disease in obesity and metabolic syndrome. By comparing hypertriglyceridemic transgenic mice expressing apolipoprotein (apo) CIII with control nontransgenic (NTg) littermates, we demonstrated that overexpression of apoCIII, independent of a high-fat diet (HFD), produces NAFLD-like features, including increased liver lipid content; decreased antioxidant power; increased expression of TNFα, TNFα receptor, cleaved caspase-1, and interleukin-1β; decreased expression of adiponectin receptor-2; and increased cell death...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28134848/insulin-production-and-resistance-in-different-models-of-diet-induced-obesity-and-metabolic-syndrome
#4
Salamah M Alwahsh, Benjamin J Dwyer, Shareen Forbes, David H van Thiel, Philip J Starkey Lewis, Giuliano Ramadori
The role of the liver and the endocrine pancreas in development of hyperinsulinemia in different types of obesity remains unclear. Sedentary rats (160 g) were fed a low-fat-diet (LFD, chow 13% kcal fat), high-fat-diet (HFD, 35% fat), or HFD+ 30% ethanol+ 30% fructose (HF-EFr, 22% fat). Overnight-fasted rats were culled after one, four or eight weeks. Pancreatic and hepatic mRNAs were isolated for subsequent RT-PCR analysis. After eight weeks, body weights increased three-fold in the LFD group, 2.8-fold in the HFD group, and 2...
January 28, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28119529/physiologic-and-genetic-evidence-links-hemopexin-to-triglycerides-in-mice-and-humans
#5
H A Lawson, M Zayed, J P Wayhart, E Fabbrini, L Love-Gregory, S Klein, C F Semenkovich
BACKGROUND/OBJECTIVES: Elevated triglycerides predict insulin resistance and vascular disease in obesity, but how the inert triglyceride molecule is related to development of metabolic disease is unknown. To pursue novel potential mediators of triglyceride-associated metabolic disease, we used a forward genetics approach involving inbred mice and translated our findings to human subjects. SUBJECTS/METHODS: Hemopexin was identified as a differentially expressed gene within a quantitative trait locus associated with serum triglycerides in an F16 advanced intercross between the LG/J and SM/J strains of mice...
January 25, 2017: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/28116779/long-term-dietary-supplementation-with-low-dose-nobiletin-ameliorates-hepatic-steatosis-insulin-resistance-and-inflammation-without-altering-fat-mass-in-diet-induced-obesity
#6
Young-Je Kim, Myung-Sook Choi, Je Tae Woo, Mi Ji Jeong, Sang Ryong Kim, Un Ju Jung
SCOPE: We evaluated the long-term effect of low-dose nobiletin (NOB), a polymethoxylated flavone, on diet-induced obesity and related metabolic disturbances. METHODS AND RESULTS: C57BL/6J mice were fed a high-fat diet (HFD, 45 kcal% fat) with or without NOB (0.02%, w/w) for 16 weeks. NOB did not alter food intake or body weight. Despite increases in fatty acid oxidation-related genes expression and enzymes activity in adipose tissue, NOB did not affect adipose tissue weight due to simultaneous increases in lipogenic genes expression and fatty acid synthase activity...
January 24, 2017: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/28112684/out-of-the-frying-pan-dietary-saturated-fat-influences-nonalcoholic-fatty-liver-disease
#7
Elizabeth Parks, Hannele Yki-Järvinen, Meredith Hawkins
Nonalcoholic fatty liver disease (NAFLD) is characterized by excess accumulation of fat in the liver. In some cases, NAFLD is also accompanied by insulin resistance, resulting in metabolic dysfunction. Dietary fat content probably influences both NAFLD and insulin resistance; however, the immediate effects of fat consumption have not been fully explored. In this issue of the JCI, Hernández et al. evaluated hepatic glucose and lipid metabolism in humans and mice following a single oral dose of saturated fat...
February 1, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28112681/acute-dietary-fat-intake-initiates-alterations-in-energy-metabolism-and-insulin-resistance
#8
Elisa Álvarez Hernández, Sabine Kahl, Anett Seelig, Paul Begovatz, Martin Irmler, Yuliya Kupriyanova, Bettina Nowotny, Peter Nowotny, Christian Herder, Cristina Barosa, Filipa Carvalho, Jan Rozman, Susanne Neschen, John G Jones, Johannes Beckers, Martin Hrabě de Angelis, Michael Roden
BACKGROUND: Dietary intake of saturated fat is a likely contributor to nonalcoholic fatty liver disease (NAFLD) and insulin resistance, but the mechanisms that initiate these abnormalities in humans remain unclear. We examined the effects of a single oral saturated fat load on insulin sensitivity, hepatic glucose metabolism, and lipid metabolism in humans. Similarly, initiating mechanisms were examined after an equivalent challenge in mice. METHODS: Fourteen lean, healthy individuals randomly received either palm oil (PO) or vehicle (VCL)...
February 1, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28106120/altered-glucose-and-lipid-homeostasis-in-liver-and-adipose-tissue-pre-dispose-inducible-nos-knockout-mice-to-insulin-resistance
#9
Babu Nageswararao Kanuri, Jitendra S Kanshana, Sanjay C Rebello, Priya Pathak, Anand P Gupta, Jiaur R Gayen, Kumaravelu Jagavelu, Madhu Dikshit
On the basis of diet induced obesity and KO mice models, nitric oxide is implied to play an important role in the initiation of dyslipidemia induced insulin resistance. However, outcomes using iNOS KO mice have so far remained inconclusive. The present study aimed to assess IR in iNOS KO mice after 5 weeks of LFD feeding by monitoring body composition, energy homeostasis, insulin sensitivity/signaling, nitrite content and gene expressions changes in the tissues. We found that body weight and fat content in KO mice were significantly higher while the respiratory exchange ratio (RER), volume of carbon dioxide (VCO2), and heat production were lower as compared to WT mice...
January 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28096081/mice-with-hyperbilirubinemia-due-to-gilbert-s-syndrome-polymorphism-are-resistant-to-hepatic-steatosis-by-decreased-serine-73-phosphorylation-of-ppar%C3%AE
#10
Terry D Hinds, Peter A Hosick, Michael W Hankins, Andrea Nestor-Kalinoski, David E Stec
Gilbert's syndrome is derived from a polymorphism (TA repeat) in the hepatic UGT1A1 gene which results in decreased conjugation and increased levels of unconjugated bilirubin. Recently, we have shown that bilirubin binds directly to the fat burning nuclear peroxisome proliferator-activated receptor α (PPARα). Additionally, we have shown that serine 73 phosphorylation (Ser(P)(73)) of PPARα decreases activity by reducing its protein levels and transcriptional activity. The aim of this study was to determine if humanized mice with the Gilbert's polymorphism (HuUGT*28) have increased PPARα activation and reduced hepatic fat accumulation...
January 17, 2017: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28090342/-1-h-mrs-measured-ectopic-fat-in-liver-and-muscle-is-associated-with-the-metabolic-syndrome-in-danish-girls-but-not-in-boys-with-overweight-and-obesity
#11
A Nissen, C E Fonvig, E Chabanova, C Bøjsøe, C Trier, O Pedersen, T Hansen, H S Thomsen, J-C Holm
BACKGROUND: The metabolic syndrome (MetS) is a complication to overweight and obesity, which can be observed already in childhood. Ectopic lipid accumulation in muscle and liver has been shown to associate with the development of insulin resistance and dyslipidemia. Thus, the interaction between MetS and ectopic fat may offer clinical relevance. OBJECTIVES: To investigate the prevalence of MetS, or components hereof, and ectopic fat accumulation in liver and skeletal muscle tissue in children, as well as interactions between these...
December 2016: Obesity Science & Practice
https://www.readbyqxmd.com/read/28077863/what-have-human-experimental-overfeeding-studies-taught-us-about-adipose-tissue-expansion-and-susceptibility-to-obesity-and-metabolic-complications
#12
REVIEW
D J Cuthbertson, T Steele, J P Wilding, J C G Halford, J A Harrold, M Hamer, F Karpe
Overfeeding experiments, in which we impose short-term positive energy balance, help unravel the cellular, physiological and behavioural adaptations to nutrient excess. These studies mimic longer-term mismatched energy expenditure and intake. There is considerable inter-individual heterogeneity in the magnitude of weight gain when exposed to similar relative caloric excess reflecting variable activation of compensatory adaptive mechanisms. Significantly, given similar relative weight gain, individuals may be protected from/predisposed to metabolic complications (insulin resistance, dyslipidaemia, hypertension), non-alcoholic fatty liver disease and cardiovascular disease...
January 12, 2017: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/28012248/sesamol-ameliorates-diet-induced-obesity-in-c57bl-6j-mice-and-suppresses-adipogenesis-in-3t3-l1-cells-via-regulating-mitochondria-lipid-metabolism
#13
Zhigang Liu, Qinglian Qiao, Yali Sun, Yuwei Chen, Bo Ren, Xuebo Liu
SCOPE: The aim of the current study was to investigate the effect of sesamol, a natural powerful antioxidant and anti-inflammatory phenol derivative of sesame oil, on adiposity and adiposity-related metabolic disturbances in mice fed with western diet, and the potential underlying mechanisms focusing on the mitochondria-lipid metabolism. METHODS & RESULTS: In the experimental model that consisted of 3 month-old C57BL/6J mice divided into 3 groups with/without sesamol in the drinking water including standard diet, high fat and high fructose diet (HFFD), and HFFD with sesamol...
December 24, 2016: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/28005939/muscle-arnt-hif1%C3%AE-is-dispensable-in-myofiber-type-determination-vascularization-and-insulin-sensitivity
#14
Pierre-Marie Badin, Danesh H Sopariwala, Sabina Lorca, Vihang A Narkar
Aryl Hydrocarbon Receptor Nuclear Translocator/ hypoxia-inducible factor 1 beta (ARNT/ HIF1β), a member of bHLH-PAS family of transcriptional factors, plays a critical role in metabolic homeostasis, insulin resistance and glucose intolerance. The contributions of ARNT in pancreas, liver and adipose tissue to energy balance through gene regulation have been described. Surprisingly, the impact of ARNT signaling in the skeletal muscles, one of the major organs involved in glucose disposal, has not been investigated, especially in type II diabetes...
2016: PloS One
https://www.readbyqxmd.com/read/27959936/a-low-dose-of-dietary-quercetin-fails-to-protect-against-the-development-of-an-obese-phenotype-in-mice
#15
Reilly T Enos, Kandy T Velázquez, Meredith S Carson, Jamie L McClellan, Prakash Nagarkatti, Mitzi Nagarkatti, J Mark Davis, E Angela Murphy
The purpose of this study was to examine the effect of a 40% high-fat diet (HFD) supplemented with a dietary attainable level of quercetin (0.02%) on body composition, adipose tissue (AT) inflammation, Non-Alcoholic Fatty-Liver Disease (NAFLD), and metabolic outcomes. Diets were administered for 16 weeks to C57BL/6J mice (n = 10/group) beginning at 4 weeks of age. Body composition and fasting blood glucose, insulin, and total cholesterol concentrations were examined intermittently. AT and liver mRNA expression (RT-PCR) of inflammatory mediators (F4/80, CD206 (AT only), CD11c (AT only) TLR-2 (AT only), TLR-4 (AT only), MCP-1, TNF-α, IL-6 (AT only), and IL-10 (AT only)) were measured along with activation of NFκB-p65, and JNK (western blot)...
2016: PloS One
https://www.readbyqxmd.com/read/27941348/protective-effects-of-2-dodecyl-6-methoxycyclohexa-2-5-diene-1-4-dione-isolated-from-averrhoa-carambola-l-oxalidaceae-roots-on-high-fat-diet-induced-obesity-and-insulin-resistance-in-mice
#16
Juman Li, Xiaojie Wei, Qiuqiao Xie, Thi Thai Hoa Pham, Jinbin Wei, Ping He, Yang Jiao, Xiaohui Xu, Thi Huong Giang Nguyen, Qingwei Wen, Renbin Huang
BACKGROUND/AIMS: The roots of Averrhoa carambola L. (Oxalidaceae) have long been used as a traditional Chinese medicine for the treatment of diabetes and diabetes-related diseases. 2-dodecyl-6-methoxycycyclohexa-2,5-1,4-dione (DMDD) has been isolated from A. carambola L. roots, and this study was carried out to investigate the potential beneficial effects of DMDD on obesity and insulin resistance induced by a high-fat diet (HFD) in mice. METHODS: C57BL/6J mice were fed a HFD for 16 weeks and orally administered DMDD (12...
2016: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/27929200/obesity-insulin-resistance-rather-than-liver-fat-increases-coagulation-factor-activities-and-expression-in-humans
#17
Susanna Lallukka, Panu K Luukkonen, You Zhou, Elina M Petäjä, Marja Leivonen, Anne Juuti, Antti Hakkarainen, Marju Orho-Melander, Nina Lundbom, Vesa M Olkkonen, Riitta Lassila, Hannele Yki-Järvinen
Increased liver fat may be caused by insulin resistance and adipose tissue inflammation or by the common I148M variant in PNPLA3 at rs738409, which lacks both of these features. We hypothesised that obesity/insulin resistance rather than liver fat increases circulating coagulation factor activities. We measured plasma prothrombin time (PT, Owren method), activated partial thromboplastin time (APTT), activities of several coagulation factors, VWF:RCo and fibrinogen, and D-dimer concentration in 92 subjects divided into groups based on insulin sensitivity [insulin-resistant ('IR') versus insulin-sensitive ('IS')] and PNPLA3 genotype (PNPLA3(148MM/MI) vs PNPLA3(148II))...
December 8, 2016: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/27916988/circulating-scd36-levels-in-patients-with-non-alcoholic-fatty-liver-disease-and-controls
#18
S Heebøll, M K Poulsen, M J Ornstrup, T N Kjær, S B Pedersen, S Nielsen, H Grønbæk, A Handberg
BACKGROUND AND OBJECTIVE: CD36 is implicated in fatty-acid uptake in multiple tissues, including hepatocytes and adipocytes. Circulating CD36 (sCD36) is increased in non-alcoholic fatty liver disease (NAFLD). We explored this association further by investigating correlations between sCD36 levels, intrahepatic lipid content and markers of obesity in NAFLD patients and controls. METHODS: In total, 111 NAFLD patients and 33 normal/overweight controls were included...
January 10, 2017: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/27908430/evaluation-of-tissue-metal-and-trace-element-content-in-a-rat-model-of-non-alcoholic-fatty-liver-disease-using-icp-drc-ms
#19
Eugenia R Gatiatulina, Elizaveta V Popova, Valentina S Polyakova, Anastasia A Skalnaya, Eduard F Agletdinov, Alexandr A Nikonorov, Anatoly V Skalny, Alexey A Tinkov
The primary objective of the study was to assess the level of metals and trace elements in liver, serum, and hair of rats with diet-induced non-alcoholic fatty liver disease (NAFLD) using inductively coupled plasma dynamic reaction cell mass spectrometer (ICP-DRC-MS). 56 female 3-months-old Wistar rats divided into two equal groups were fed either standard (10% calories from fat) or high-fat high-carbohydrate diet (60% calories from fat in chow and 10% sucrose solution) for 6 weeks. Serum was examined for insulin resistance markers, lipid profile, and alanine aminotransferase (ALT) activity...
January 2017: Journal of Trace Elements in Medicine and Biology
https://www.readbyqxmd.com/read/27906092/alterations-to-mtorc1-signaling-in-the-skeletal-muscle-differentially-affect-whole-body-metabolism
#20
Maitea Guridi, Barbara Kupr, Klaas Romanino, Shuo Lin, Denis Falcetta, Lionel Tintignac, Markus A Rüegg
BACKGROUND: The mammalian target of rapamycin complex 1 (mTORC1) is a central node in a network of signaling pathways controlling cell growth and survival. This multiprotein complex integrates external signals and affects different nutrient pathways in various organs. However, it is not clear how alterations of mTORC1 signaling in skeletal muscle affect whole-body metabolism. RESULTS: We characterized the metabolic phenotype of young and old raptor muscle knock-out (RAmKO) and TSC1 muscle knock-out (TSCmKO) mice, where mTORC1 activity in skeletal muscle is inhibited or constitutively activated, respectively...
March 21, 2016: Skeletal Muscle
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