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liver fat content and insulin resistance

Sandip K Boss, Irina Hutson, Charles Harris
Exogenous glucocorticoid (GC) administration results in hyperglycemia, insulin resistance, hepatic dyslipidemia and hypertension, a constellation of findings known as Cushing's syndrome. These effects are mediated by the glucocorticoid receptor (GR). Since GR activation in liver and adipose has been implicated in metabolic syndrome we wanted to determine the role of GR in these tissues in the development of metabolic syndrome. Since GRKO mice (whole body KO) exhibit perinatal lethality due to respiratory failure, we generated tissue specific (liver or adipose) GRKO mice using cre-lox technology...
October 18, 2016: Endocrinology
Myung-Shik Lee
Low-grade systemic inflammation in adipose tissues or liver, is an important etiologic factor in insulin resistance. LPS is an important element causing such metabolic inflammation, and intestinal flora is considered a major source of systemic LPS. We studied changes of intestinal microbiota associated with high-fat diet (HFD) that causes insulin resistance and metabolic stress. 16S rRNA gene sequencing showed that HFD significantly decreased the abundance of a mucin-degrading bacterium Akkermansia muciniphila compared to control diet...
September 2016: Journal of Hypertension
Sini Heinonen, Maheswary Muniandy, Jana Buzkova, Adil Mardinoglu, Amaia Rodríguez, Gema Frühbeck, Antti Hakkarainen, Jesper Lundbom, Nina Lundbom, Jaakko Kaprio, Aila Rissanen, Kirsi H Pietiläinen
AIMS/HYPOTHESIS: Low mitochondrial activity in adipose tissue is suggested to be an underlying factor in obesity and its metabolic complications. We aimed to find out whether mitochondrial measures are downregulated in obesity also in isolated adipocytes. METHODS: We studied young adult monozygotic (MZ) twin pairs discordant (n = 14, intrapair difference ΔBMI ≥ 3 kg/m(2)) and concordant (n = 5, ΔBMI < 3 kg/m(2)) for BMI, identified from ten birth cohorts of 22- to 36-year-old Finnish twins...
October 12, 2016: Diabetologia
Jennifer Chi Lo, Anne E O'Connor, Zane B Andrews, Camden Lo, Tony Tiganis, Matthew J Watt, Moira K O'Bryan
Fatty liver, or hepatic steatosis, is an alarmingly common pathology in western societies, in large part because if left unheaded it can lead to life-threatening forms of non-alcoholic fatty liver disease, including non-alcoholic steatohepatitis, fibrosis, cirrhosis and hepatocellular carcinoma. As such, it is essential that we attain a greater understanding of the pathways that control energy partitioning in the liver, and ultimately how they are impacted by environmental factors. Herein, we define the essential requirement for a member of the RAB-like clade of small GTPases, RABL2, in fatty acid metabolism including in microtubule-associated mitochondrial movement within the liver...
October 12, 2016: Endocrinology
Tsuyoshi Chiba, Sachina Suzuki, Yoko Sato, Tatsuki Itoh, Keizo Umegaki
AIM: Non-alcoholic steatohepatitis (NASH) is a globally recognized liver disease. A methionine- and choline-deficient diet is used to induce NASH in mice; however, this diet also causes severe body weight loss. To resolve this issue, we examined the effects of methionine content in a high-fat and choline-deficient (HFCD) diet on body weight and the development of NASH in mice. METHODS: C57BL/6J mice (male, 10 weeks of age) were fed an L-amino acid rodent (control) diet, high-fat (HF) diet, or HFCD diet containing various amounts of methionine (0...
2016: PloS One
Núria Taltavull, Rosa Ras, Sílvia Mariné, Marta Romeu, Montserrat Giralt, Lucía Méndez, Isabel Medina, Sara Ramos-Romero, Josep L Torres, M Rosa Nogués
A high intake of fat and sucrose can dramatically increase bioactive lipids such as ceramides in tissues. Ceramides regulate several steps in the insulin signal pathway. The effects of n-3 PUFA on insulin resistance are inconsistent, especially in liver. We investigated the effect of n-3 PUFA (EPA/DHA 1 : 1) from fish oil on hepatic ceramides in a pre-diabetic animal model. Three groups of rats were fed standard feed, high fat high sucrose feed (HFHS) or HFHS enriched with n-3 PUFA. We investigated by lipidomic analysis how supplementation of a HFHS diet with n-3 PUFA modifies the hepatic ceramide profile triggered by a HFHS diet...
September 14, 2016: Food & Function
A J Pantophlet, W J J Gerrits, R J Vonk, J J G C van den Borne
In veal calves, the major portion of digestible energy intake originates from milk replacer (MR), with lactose and fat contributing approximately 45 and 35%, respectively. In veal calves older than 4 mo, prolonged high intakes of MR may lead to problems with glucose homeostasis and insulin sensitivity, ultimately resulting in sustained insulin resistance, hepatic steatosis, and impaired animal performance. The contribution of each of the dietary energy sources (lactose and fat) to deteriorated glucose homeostasis and insulin resistance is currently unknown...
October 5, 2016: Journal of Dairy Science
Stefan Z Lutz, Andreas Peter, Fausto Machicao, Apostolia Lamprinou, Jürgen Machann, Fritz Schick, Ingmar Königsrainer, Alfred Königsrainer, Andreas Fritsche, Harald Staiger, Hans-Ulrich Häring, Norbert Stefan, Konstantinos Kantartzis
CONTEXT/OBJECTIVE: Acute pharmacological inhibition of 11β-hydroxysteroid-dehydrogenase 1 (11β-HSD1), which converts cortisone into the much more potent cortisol in peripheral tissues, results in reduction of total-, visceral- and liver fat, but not of insulin resistance. We now investigated whether lifelong alterations of 11β-HSD1 activity similarly affect these cardiometabolic risk parameters, by studying single nucleotide polymorphisms (SNPs) in the 11β-HSD1-coding gene (HSD11B1)...
October 7, 2016: Journal of Clinical Endocrinology and Metabolism
U Smith, B B Kahn
Obesity, the major cause of the current global epidemic of type 2 diabetes (T2D), induces insulin resistance in peripheral insulin target tissues. Several mechanisms have been identified related to cross-talk between adipose tissue, skeletal muscle and liver. These mechanisms involve both increased free fatty acid release and altered secretion of adipokines from adipose tissue. A major determinant of metabolic health is the ability of subcutaneous adipose tissue (SAT) to store excess fat rather than allowing it to accumulate in ectopic depots including liver (i...
October 3, 2016: Journal of Internal Medicine
Myung-Shik Lee
Low-grade systemic inflammation in adipose tissues or liver, is an important etiologic factor in insulin resistance. LPS is an important element causing such metabolic inflammation, and intestinal flora is considered a major source of systemic LPS. We studied changes of intestinal microbiota associated with high-fat diet (HFD) that causes insulin resistance and metabolic stress. 16S rRNA gene sequencing showed that HFD significantly decreased the abundance of a mucin-degrading bacterium Akkermansia muciniphila compared to control diet...
September 2016: Journal of Hypertension
Nirali Shah, Henry H Ruiz, Usman Zafar, Kalmon D Post, Christoph Buettner, Eliza B Geer
CONTEXT: Inflammation contributes to the development of metabolic and cardiovascular disease. Cushing's disease (CD), a state of chronic glucocorticoid (GC) excess characterized by visceral obesity and insulin resistance, may be associated with increased systemic inflammation. Cardiovascular mortality in CD remains elevated even after successful remission. It is unclear whether a chronic low-grade inflammatory state persists even after remission of CD, which may account for the increased CVD mortality...
September 15, 2016: Clinical Endocrinology
Yoshiyuki Sugaya, Hiroaki Satoh
BACKGROUND: Hepatic steatosis is strongly associated with insulin resistance. It has been reported that G0S2 inhibited the lipolytic activity of adipose triglyceride lipase (ATGL), which is a major hepatic lipase as well as in adipocytes. Moreover, we confirmed that G0S2 protein contents were increased in the livers of high fat diet (HFD)-fed rats. We investigated the effect of hepatic G0S2 on insulin sensitivity in male Wistar rats. METHODS: Male Wistar rats were fed 60% HFD for 4 weeks...
September 14, 2016: Journal of Diabetes
Inês Sousa-Lima, Shin-Young Park, Michelle Chung, Hyun Ju Jung, Min-Cheol Kang, Joana M Gaspar, Ji A Seo, M Paula Macedo, Kyong Soo Park, Christos Mantzoros, Seung-Hoon Lee, Young-Bum Kim
Methylsulfonylmethane (MSM), an organosulfur compound, has been used as a dietary supplement that can improve various metabolic diseases. However, the effect of MSM on obesity-linked metabolic disorders remains unclear. The goal of the current study is to determine whether MSM has beneficial effects on glucose and lipid homeostasis in obesity-associated pathophysiologic states. High-fat diet-induced obese (DIO) and genetically obese diabetic db/db mice treated with MSM (1%-5% v/v, by drinking water) were studied...
October 2016: Metabolism: Clinical and Experimental
Magdalene K Montgomery, Simon H J Brown, Xin Y Lim, Corrine E Fiveash, Brenna Osborne, Nicholas L Bentley, Jeremy P Braude, Todd W Mitchell, Adelle C F Coster, Anthony S Don, Gregory J Cooney, Carsten Schmitz-Peiffer, Nigel Turner
In a recent study, we showed that in response to high fat feeding C57BL/6, 129X1, DBA/2 and FVB/N mice all developed glucose intolerance, while BALB/c mice displayed minimal deterioration in glucose tolerance and insulin action. Lipidomic analysis of livers across these five strains has revealed marked strain-specific differences in ceramide (Cer) and sphingomyelin (SM) species with high-fat feeding; with increases in C16-C22 (long-chain) and reductions in C>22 (very long-chain) Cer and SM species observed in the four strains that developed HFD-induced glucose intolerance...
August 31, 2016: Biochimica et Biophysica Acta
Gonzalo Torres-Villalobos, Nashla Hamdan-Pérez, Andrea Díaz-Villaseñor, Armando R Tovar, Ivan Torre-Villalvazo, Guillermo Ordaz-Nava, Sofía Morán-Ramos, Lilia G Noriega, Braulio Martínez-Benítez, Alejandro López-Garibay, Samuel Torres-Landa, Juan C Ceballos-Cantú, Claudia Tovar-Palacio, Elizabeth Figueroa-Juárez, Marcia Hiriart, Roberto Medina-Santillán, Carmen Castillo-Hernández, Nimbe Torres
Long-term dietary and pharmacological treatments for obesity have been questioned, particularly in individuals with severe obesity, so a new approach may involve adipose tissue transplants, particularly autologous transplants. Thus, the aim of this study was to evaluate the metabolic effects of autologous subcutaneous adipose tissue (SAT) transplants into two specific intraabdominal cavity sites (omental and retroperitoneal) after 90 days. The study was performed using two different diet-induced obesity (DIO) rat models: one using a high-fat diet (HFD) and the other using a high-carbohydrate diet (HCHD)...
September 2016: Physiological Reports
Keita Chikamoto, Hirofumi Misu, Hiroaki Takayama, Akihiro Kikuchi, Kiyo-Aki Ishii, Fei Lan, Noboru Takata, Natsumi Tajima-Shirasaki, Yumie Takeshita, Hirohiko Tsugane, Shuichi Kaneko, Seiichi Matsugo, Toshinari Takamura
Dieting often leads to body weight cycling involving repeated weight loss and regain. However, little information is available regarding rapid-response serum markers of overnutrition that predict body weight alterations during weight cycling. Here, we report the rapid response of serum leukocyte cell-derived chemotaxin 2 (LECT2), a hepatokine that induces insulin resistance in skeletal muscle, during diet-induced weight cycling in mice. A switch from a high-fat diet (HFD) to a regular diet (RD) in obese mice gradually decreased body weight but rapidly decreased serum LECT2 levels within 10 days...
September 23, 2016: Biochemical and Biophysical Research Communications
Yan Liu, Di Mu, Hongen Chen, Di Li, Jiayi Song, Yuan Zhong, Min Xia
CONTEXT AND OBJECTIVE: Elevated serum retinol binding protein 4 (RBP4) has been implicated in insulin resistant and nonalcoholic fatty liver disease (NAFLD) subjects, however, the molecular mechanism of RBP4 in NAFLD remains obscure. DESIGN AND PARTICIPANTS: Hepatic RBP4 mRNA level and its association with lipid accumulation were examined in NAFLD patients and mouse model. Furthermore, human RBP4 overexpressing (RBP4-Tg) mice were metabolically phenotyped following either a regular chow (RC) or high-fat diet (HFD)...
August 9, 2016: Journal of Clinical Endocrinology and Metabolism
Radiša Prodanović, Goran Korićanac, Ivan Vujanac, Ana Djordjević, Marija Pantelić, Snježana Romić, Zoran Stanimirović, Danijela Kirovski
We investigated the hypothesis that obesity in dairy cows enhanced expression of proteins involved in hepatic fatty acid uptake and metabolism. Sixteen Holstein-Friesian close-up cows were divided into 2 equal groups based on their body condition score (BCS) as optimal (3.25≤BCS≤3.5) and high (4.0≤BCS≤4.25). Intravenous glucose tolerance test (GTT) and liver biopsies were carried out at day 10 before calving. Blood samples were collected before (basal) and after glucose infusion, and glucose, insulin and non-esterified fatty acid (NEFA) levels were determined at each sample point...
August 2016: Research in Veterinary Science
Pegah Golabi, Cameron T Locklear, Patrick Austin, Sophie Afdhal, Melinda Byrns, Lynn Gerber, Zobair M Younossi
AIM: To investigate the efficacy of exercise interventions on hepatic fat mobilization in non-alcoholic fatty liver disease (NAFLD) patients. METHODS: Ovid-Medline, PubMed, EMBASE and Cochrane database were searched for randomized trials and prospective cohort studies in adults aged ≥ 18 which investigated the effects of at least 8 wk of exercise only or combination with diet on NAFLD from 2010 to 2016. The search terms used to identify articles, in which exercise was clearly described by type, duration, intensity and frequency were: "NASH", "NAFLD", "non-alcoholic steatohepatitis", "non-alcoholic fatty liver disease", "fat", "steatosis", "diet", "exercise", "MR spectroscopy" and "liver biopsy"...
July 21, 2016: World Journal of Gastroenterology: WJG
Rosamar E F Rezende, Sebastião M B Duarte, Jose T Stefano, Hamilton Roschel, Bruno Gualano, Ana L de Sá Pinto, Denise C P Vezozzo, Flair J Carrilho, Claudia P Oliveira
OBJECTIVE: The aim of the study was to evaluate the effectiveness of aerobic physical activity in reducing the frequency of hepatic steatosis and metabolic and cardiovascular risk in postmenopausal women with nonalcoholic fatty liver disease (NAFLD). METHODS: Forty sedentary postmenopausal women (mean age 55.3 ± 8.0 y) with biopsy-proven NAFLD were randomly divided into two groups: an exercising group (19 participants) and a control group (nonexercising, 21 participants)...
August 2016: Menopause: the Journal of the North American Menopause Society
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