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Obesity, mice

Michele Alves-Bezerra, Yingxia Li, Mariana Acuña, Anna A Ivanova, Kathleen E Corey, Eric A Ortlund, David E Cohen
In non-alcoholic fatty liver disease (NAFLD), triglycerides accumulate within the liver because the rates of fatty acid accrual by uptake from plasma and de novo synthesis exceed elimination by mitochondrial oxidation and secretion as VLDL-triglycerides. Thioesterase superfamily member 2 (Them2) is an acyl-CoA thioesterase that catalyzes the hydrolysis of fatty acyl-CoAs into free fatty acids plus CoASH. Them2 is highly expressed in the liver, as well as other oxidative tissues. Mice globally lacking Them2 are resistant to diet-induced obesity and hepatic steatosis, and exhibit improved glucose homeostasis...
December 5, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Pei-Sheng Lee, Chia-Yi Teng, Nagabhushanam Kalyanam, Chi-Tang Ho, Min-Hsiung Pan
SCOPE: Obesity has become a major health problem worldwide and is associated with low-grade chronic inflammation and intestinal dysbiosis. This study was conducted to investigate the chemopreventive effects of garcinol, a polyisoprenylated benzophenone derivative isolated from the fruit rind of Garcinia indica. We sought to delineate how garcinol protects against obesity in high-fat diet (HFD)-induced mice and determine whether its anti-obesity effects are related to gut microbiota. METHODS AND RESULTS: The results showed that garcinol reduced HFD-fed mice body weight gain and relative visceral adipose tissue fat weight in a dose-dependent manner...
December 5, 2018: Molecular Nutrition & Food Research
Fabio Ciccarone, Serena Castelli, Laura Ioannilli, Maria Rosa Ciriolo
SCOPE: Epigenetic aberrations caused by environmental factors and lifestyle choices have been associated with the development of a number of pathologies including cardiovascular disorders. However, whether obesity-related heart dysfunction can occur via epigenetic mechanisms is largely undisclosed. The manifested role of DNA hydroxymethylation in heart pathophysiology prompted us to investigate its levels/machinery in heart of mice fed with high fat diet (HFD) and its possible relation with genes linked to obesity-associated cardiac remodelling...
December 4, 2018: Molecular Nutrition & Food Research
Hee-Jeong Kim, Bohkyung Kim, Eun-Gyung Mun, Soon-Yeon Jeong, Youn-Soo Cha
BACKGROUND/OBJECTIVES: Ginger, a root vegetable, is known to have antioxidant and antiobesity effects. Preparation, such as by steaming, can affect the chemical composition of prepared root vegetables or herbs and can change their functional activities. In the present study, we investigated the protective effects of steamed ginger against oxidative stress and steatosis in C57BL/6J mice fed a high-fat diet. MATERIALS/METHODS: The levels of polyphenols and flavonoids in two different extracts of steamed ginger, i...
December 2018: Nutrition Research and Practice
Yunkyoung Lee, Hyunhee Oh, Myoungsook Lee
BACKGROUND/OBJECTIVES: Gelidium amansii ( GA ) contains plenty of agars and various biological substances, which make them a popular functional food to control body weight in previous studies. Unlike previous studies focused on agar in GA, objectives of this study were to investigate the effects of agar-free GA extract ( AfGAE ) on preventive and treatment models by using diets-induced obese (DIO) C57BL/6J mice. MATERIALS/METHODS: Af GAE were used to test their effects on the prevention ( Exp-1 ) and treatment ( Exp-2 ) against obesity after pilot study in DIO mice...
December 2018: Nutrition Research and Practice
Asha Recino, Shu Uin Gan, Kian Chuan Sia, Yvonne Sawyer, Jenny Trendell, Richard Kay, Fiona M Gribble, Frank Reimann, Rob Foale, Maria Notaridou, Nick Holmes, Andrew Lever, Kok Onn Lee, Amit Nathwani, Anne Cooke, Roy Calne, Maja Wallberg
We report the restoration of euglycaemia in chemically induced diabetic C57BL/6 mice and spontaneously diabetic Non Obese Diabetic (NOD) mice by intravenous systemic administration of a single-stranded adeno-associated virus (ssAAV2/8) codon optimised (co) vector encoding furin cleavable human proinsulin under a liver-specific promoter. There were no immunological barriers to efficacy of insulin gene therapy in chemically induced C57BL/6 mice, which enjoyed long-lasting correction of hyperglycaemia after therapy, up to 250 days...
December 4, 2018: Gene Therapy
Simona Terzo, Gaetano Felice Caldara, Vincenzo Ferrantelli, Roberto Puleio, Giovanni Cassata, Flavia Mulè, Antonella Amato
Pistachios contain beneficial substances such as unsaturated fatty acids, phytosterols, and polyphenols. In the present study, we investigated if pistachio consumption is able to prevent or to revert hyperglycemia, dyslipidemia, hepatic steatosis, and adipose tissue morphological alterations caused by high fat diet (HFD) in the mouse. Moreover, the impact of pistachio intake on the mRNA expression of peroxisome proliferator-activated receptor γ ( PPAR-γ ), fatty acid transport proteins ( FAT-P ), fatty acid synthase ( FAS ), stearoyl-CoA desaturase ( SCD1 ), and sterol regulatory element-binding transcription factor-1c ( SREBP-1c ) in liver and adipose tissue was also analyzed...
December 1, 2018: Nutrients
Jiyeon Kim, Jinho An, Heetae Lee, Kyungjae Kim, Su Jung Lee, Hye Ran Choi, Ji-Wung Kwon, Tae-Bum Lee, Youngcheon Song, Hyunseok Kong
Metabolic syndrome is characterized by a combination of several metabolic disorders, including obesity, hyperglycemia, and hyperlipidemia. A simultaneous occurrence is one of the most crucial features of metabolic syndrome; therefore, we selected an animal model in which this would be reflected. We fed C57BL/6N mice a high-fat diet for 23 weeks to develop metabolic syndrome and examined the efficacy of Rubus occidentalis (RO) for hyperglycemia and hypercholesterolemia. Oral administration of RO for 16 weeks improved hyperglycemia as indicated by significantly decreased fasting glucose levels and a glucose tolerance test...
December 1, 2018: Nutrients
Simon T Bond, Sarah C Moody, Yingying Liu, Mete Civelek, Claudio J Villanueva, Paul Gregorevic, Bronwyn A Kingwell, Andrea L Hevener, Aldons J Lusis, Darren C Henstridge, Anna C Calkin, Brian G Drew
Mitochondrial dynamics refers to the constant remodelling of mitochondrial populations by multiple cellular pathways which help maintain mitochondrial health and function. Disruptions to mitochondrial dynamics often leads to mitochondrial dysfunction, which is frequently associated with disease in rodents and humans. Consistent with this, obesity is associated with reduced mitochondrial function in white adipose tissue, partly via alterations in mitochondrial dynamics. Several proteins are known to regulate mitochondrial dynamics including the E3 ubiquitin ligase MARCH5; however, the role of these proteins in adipocytes has been poorly studied...
December 4, 2018: American Journal of Physiology. Endocrinology and Metabolism
Russell Emmons, Guanying Xu, Diego Hernandez-Saavedra, Adam Kriska, Yuan-Xiang Pan, Hong Chen, Michael De Lisio
Obesity-induced inflammation associated with increased risk for colorectal cancer (CRC). The role of diet and exercise in modulating increased CRC risk in obesity, and the potential role of altered hematopoiesis as a contributor to these effects remain unknown. The purpose of this study was to examine how weight loss induced during CRC induction with or without exercise alter CRC initiation and their relationship to altered hematopoiesis. Mice consumed either a control (CON) or high fat diet to induce obesity...
December 4, 2018: American Journal of Physiology. Endocrinology and Metabolism
Guoqing Wu, Yanan Wang, Yuhui Yang, Yonghui Shi, Jin Sun, Yunchong Xu, Tingyu Luo, Guowei Le
SCOPE: Dietary methionine restriction (MR) promotes multi-faceted health benefits. Moreover, lower rate of protein synthesis by dietary MR is associated with life span extension. The goal of this work is to explore how dietary MR would affect protein metabolism in a mouse model of high-fat diet-induced obesity (DIO). METHODS AND RESULTS: DIO mice (male C57BL/6) were subjected to dietary MR for 22 weeks. High-throughput sequencing technology, qRT-PCR analysis, and the dual luciferase reporter assay were performed to verify that MiR-328-3p directly targets cystathionine γ-lyase (CSE) to modulate endogenous H2 S production...
December 4, 2018: Molecular Nutrition & Food Research
Hongsuk Park, Anyuan He, Min Tan, Jordan M Johnson, John M Dean, Terri A Pietka, Yali Chen, Xiangyu Zhang, Fong-Fu Hsu, Babak Razani, Katsuhiko Funai, Irfan J Lodhi
Peroxisomes perform essential functions in lipid metabolism, including fatty acid oxidation and plasmalogen synthesis. Here, we describe a role for peroxisomal lipid metabolism in mitochondrial dynamics in brown and beige adipocytes. Adipose tissue peroxisomal biogenesis was induced in response to cold exposure through activation of the thermogenic co-regulator PRDM16. Adipose-specific knockout of the peroxisomal biogenesis factor Pex16 (Pex16-AKO) in mice impaired cold tolerance, decreased energy expenditure, and increased diet-induced obesity...
December 4, 2018: Journal of Clinical Investigation
Martina Rudnicki, Ghoncheh Abdifarkosh, Emmanuel Nwadozi, Sofhia V Ramos, Armin Makki, Diane M Sepa-Kishi, Rolando B Ceddia, Christopher Gr Perry, Emilie Roudier, Tara L Haas
Impaired angiogenesis is a hallmark of metabolically dysfunctional adipose tissue in obesity. However, the underlying mechanisms restricting angiogenesis within this context remain ill-defined. Here, we demonstrate that induced endothelial-specific depletion of the transcription factor Forkhead Box O1 (FoxO1) in male mice led to increased vascular density in adipose tissue. Upon high-fat diet feeding, endothelial cell FoxO1-deficient mice exhibited even greater vascular remodeling in the visceral adipose depot, which was paralleled with a healthier adipose tissue expansion, higher glucose tolerance and lower fasting glycemia concomitant with enhanced lactate levels...
December 4, 2018: ELife
Alpna Tyagi, Christy U Nguyen, Thomas Chong, Cole R Michel, Kristofer S Fritz, Nichole Reisdorph, Leslie Knaub, Jane E B Reusch, Subbiah Pugazhenthi
SIRT3, the primary mitochondrial deacetylase, plays a significant role in enhancing the function of mitochondrial proteins. Downregulation of SIRT3 is a key component of metabolic syndrome, a precondition for obesity, diabetes and cardiovascular diseases. In this study, we examined the effects of brain mitochondrial protein hyperacetylation in western diet-fed Sirt3-/- mice, a model for metabolic syndrome. Brain mitochondrial proteins were hyperacetylated, following western diet feeding and Sirt3 deletion. To identity these hyperacetylated proteins, we performed a comprehensive acetylome analysis by label-free tandem mass spectrometry...
December 3, 2018: Scientific Reports
Amy Christensen, Christian J Pike
Development of Alzheimer's disease (AD) is regulated by interactive effects of genetic and environmental risk factors. The most significant genetic risk factor for AD is the ε4 allele of apolipoprotein E ( APOE4), which has been shown to exert greater AD risk in women. An important modifiable AD risk factor is obesity and its associated metabolic dysfunctions. Whether APOE genotype might interact with obesity in females to regulate AD pathogenesis is unclear. To investigate this issue, we studied the effects of Western diet (WD) on female EFAD mice, a transgenic mouse model of AD that includes human APOE alleles ε3 (E3FAD) and ε4 (E4FAD)...
December 3, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Ashley Untereiner, Shaaban Abdo, Alpana Bhattacharjee, Himaben Gohil, Farzaneh Pourasgari, Neke Ibeh, Mi Lai, Battsetseg Batchuluun, Anthony Wong, Nicholas Khuu, Ying Liu, Dana Al Rijjal, Neil Winegarden, Carl Virtanen, Beverley A Orser, Over Cabrera, Gabor Varga, Jonathan Rocheleau, Feihan F Dai, Michael B Wheeler
γ-Aminobutyric acid (GABA) administration has been shown to increase β-cell mass, leading to a reversal of type 1 diabetes in mice. Whether GABA has any effect on β cells of healthy and prediabetic/glucose-intolerant obese mice remains unknown. In the present study, we show that oral GABA administration ( ad libitum) to mice indeed increased pancreatic β-cell mass, which led to a modest enhancement in insulin secretion and glucose tolerance. However, GABA treatment did not further increase insulin-positive islet area in high fat diet-fed mice and was unable to prevent or reverse glucose intolerance and insulin resistance...
December 3, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Célia Fourrier, Clémentine Bosch-Bouju, Raphaël Boursereau, Julie Sauvant, Agnès Aubert, Lucile Capuron, Guillaume Ferreira, Sophie Layé, Nathalie Castanon
Although the high prevalence of anxiety in obesity increasingly emerges as significant risk factor for related severe health complications, the underlying pathophysiological mechanisms remain poorly understood. Considering that chronic inflammation is a key component of obesity and is well known to impact brain function and emotional behavior, we hypothesized that it may similarly contribute to the development of obesity-related anxiety. This hypothesis was experimentally tested by measuring whether chronic food restriction, a procedure known to reduce inflammation, or chronic anti-inflammatory treatment with ibuprofen improved anxiety-like behavior and concomitantly decreased peripheral and/or hippocampal inflammation characterizing a model of severe obesity, the db/db mice...
November 30, 2018: Brain, Behavior, and Immunity
Miriam Thomalla, Andreas Schmid, Elena Neumann, Petra Ina Pfefferle, Ulf Mueller-Ladner, Andreas Schäffler, Thomas Karrasch
Adipocytes express various pattern recognition receptors (PRRs) such as Toll-like receptors (TLRs) and actively participate in anti-bacterial and anti-viral host defence. Obesity is associated with adipose tissue PRR expression. The potential role of Toll-like receptor 9 (TLR9) in adipocytes has not yet been investigated. Here, we evaluated TLR9 expression during adipocyte differentiation (AD) of 3T3-L1 adipocytes, in primary murine adipocytes and in different murine and human adipose tissue depots by real-time PCR, immunocytochemistry and immunohistochemistry...
December 1, 2018: Journal of Endocrinology
Jie Liu, Grzegorz Godlewski, Tony Jourdan, Ziyi Liu, Resat Cinar, Keming Xiong, George Kunos
Endocannabinoids promote energy conservation in obesity, whereas cannabinoid-1 receptor (CB1 R) blockade reverses body weight gain and insulin resistance and increases energy expenditure. Here we investigated the molecular mechanisms of the catabolic effects of CB1 R blockade in the liver. Exposure of primary mouse hepatocytes and HepG2 cells to the CB1 R agonist ACEA inhibited the expression of Sirt1 and Rictor, a component of mTORC2, and suppressed insulin-induced Akt phosphorylation at ser473. These effects were reversed by peripheral CB1 R antagonist JD5037 in control hepatocytes but not in hepatocytes deficient in Sirt1 and/or Rictor, indicating that these two proteins are required for the CB1 R-mediated inhibition of insulin signaling...
December 1, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Song-Yun Zhang, Su-Xiao Ji, Xiao-Mei Bai, Fang Yuan, Li-Hui Zhang, Jie Li
Numerous epidemiological studies have shown that diabetes mellitus (DM) is associated with dementia and cognition decline. However, there is currently no effective treatment for diabetes-induced cognitive dysfunction. The neuroprotective effect of L-3-n-butylphthalide (L-NBP) has been demonstrated in vascular dementia animal models. The purpose of this study was to determine whether L-NBP can ameliorate cognitive deficits in db/db mice, a model of obesity and type 2 diabetes. The mice were administered with vehicle or L-NBP (120 mg/kg) by gavage daily for 6 weeks...
December 1, 2018: Metabolic Brain Disease
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