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Obesity, mouse, mice

Di Shao, Chunxiang Yao, Maya H Kim, Jessica Fry, Richard A Cohen, Catherine E Costello, Reiko Matsui, Francesca Seta, Mark E McComb, Markus M Bachschmid
Sirtuin-1 (SirT1) catalyzes NAD+ -dependent protein lysine deacetylation and is a critical regulator of energy and lipid metabolism, mitochondrial biogenesis, apoptosis, and senescence. Activation of SirT1 mitigates metabolic perturbations associated with diabetes and obesity. Pharmacologic molecules, cellular redox, and nutritional states can regulate SirT1 activity. Technical barriers against measuring endogenous SirT1 activity have limited characterization of SirT1 in disease and its activation by small molecules...
March 5, 2019: Redox Biology
Peixin Li, Zhijian Rao, Brenton Laing, Wyatt Paul Bunner, Taylor Landry, Amber Prete, Yuan Yuan, Zhong-Tao Zhang, Hu Huang
Vertical sleeve gastrectomy (VSG) is an effective surgery to treat obesity and diabetes. However, the direct effect of VSG on metabolic functions is not fully understood. We aimed to investigate if alterations in hypothalamic neurons were linked with perturbations in liver metabolism after VSG in an energy intake-controlled obese mouse model. C57BL/6 and hrNPY-GFP reporter mice received HFD for 12 weeks and were then divided into three groups: Sham (ad lib), sham (pair-fed) with VSG, and VSG. Food intake was measured daily, and blood glucose levels were measured before and after the study...
March 1, 2019: Journal of Endocrinology
Kembra Albracht-Schulte, Samantha Gonzalez, Abigail Jackson, Savanna Wilson, Latha Ramalingam, Nishan S Kalupahana, Naima Moustaid-Moussa
The prevalence of nonalcoholic fatty liver disease (NAFLD) is increasing worldwide, concurrent with increased obesity. Thus, there is urgent need for research that can lead to effective NAFLD prevention/treatment strategies. Omega-3 polyunsaturated fatty acids (n-3 PUFAs), including eicosapentaenoic acid (EPA), improve inflammation- and dyslipidemia-related metabolic disorders; however, mechanisms mediating the benefits of n-3 PUFAs in NAFLD treatment are less understood. We previously reported that EPA reversed obesity-induced hepatic steatosis in high-fat (HF)-fed B6 mice...
March 12, 2019: Nutrients
Hyon-Seung Yi, So Yeon Kim, Jung Tae Kim, Young-Sun Lee, Ji Sun Moon, Mingyo Kim, Yea Eun Kang, Kyong Hye Joung, Ju Hee Lee, Hyun Jin Kim, Kwangsik Chun, Minho Shong, Bon Jeong Ku
Chronic inflammation is a driving force for the development of metabolic disease including diabetes and obesity. However, the functional characteristics of T-cell senescence in the abnormal glucose homeostasis are not fully understood. We studied the patients visiting a hospital for routine health check-ups, who were divided into two groups: normal controls and people with prediabetes. Gene expression profiling of peripheral blood mononuclear cells from normal controls and patients with type 2 diabetes was undertaken using microarray analysis...
March 13, 2019: Cell Death & Disease
Brett L Ecker, Jun Y Lee, Christopher J Sterner, Aaron C Solomon, Dhruv K Pant, Fei Shen, Javier Peraza, Lauren Vaught, Samyukta Mahendra, George K Belka, Tien-Chi Pan, Kathryn H Schmitz, Lewis A Chodosh
BACKGROUND: Obesity is associated with an increased risk of breast cancer recurrence and cancer death. Recurrent cancers arise from the pool of residual tumor cells, or minimal residual disease (MRD), that survives primary treatment and persists in the host. Whether the association of obesity with recurrence risk is causal is unknown, and the impact of obesity on MRD and breast cancer recurrence has not been reported in humans or in animal models. METHODS: Doxycycline-inducible primary mammary tumors were generated in intact MMTV-rtTA;TetO-HER2/neu (MTB/TAN) mice or orthotopic recipients fed a high-fat diet (HFD; 60% kcal from fat) or a control low-fat diet (LFD; 10% kcal from fat)...
March 13, 2019: Breast Cancer Research: BCR
Raquel Santana da Cruz, Johan Clarke, Ana Cristina Curi, Aseel Al-Yawar, Lu Jin, Ali Baird, Idalia Cruz, Bhaskar V Kallakury, Sonia de Assis
Epidemiological studies suggest that timing of obesity onset (and underlying metabolic dysfunction) is important in determining pancreatic cancer rates: Early and young adult abdominal overweight/obesity is more strongly associated with this cancer than obesity that develops later in life. Parental obesity and overweight is associated with metabolic dysfunction and obesity in their children. Here, we evaluated the impact of parental overweight on offspring's susceptibility of pancreatic cancer using the P48Cre/+ /KrasG120/+ mouse model...
March 1, 2019: Endocrine-related Cancer
Carsten A Raabe, Reinhard Voss, Delf-Magnus Kummerfeld, Juergen Brosius, Chenna R Galiveti, Anna Wolters, Jochen Seggewiss, Andreas Huge, Boris V Skryabin, Timofey S Rozhdestvensky
Serotonin 5-HT2C receptor is a G-protein coupled excitatory receptor that regulates several biochemical pathways and has been implicated in obesity, mental state, sleep cycles, autism, neuropsychiatric disorders and neurodegenerative diseases. The activity of 5-HT2CR is regulated via alternative splicing and A to I editing of exon Vb of its pre-mRNA. Snord115 is a small nucleolar RNA that is expressed in mouse neurons and displays an 18-nucleotide base complementary to exon Vb of 5-HT2CR pre-mRNA. For almost two decades this putative guide element of Snord115 has wandered like a ghost through the literature in attempts to elucidate the biological significance of this complementarity...
March 12, 2019: Scientific Reports
Yoshitake Cho, Shizuko Tachibana, Bethany C Hazen, James J Moresco, John R Yates, Bernard Kok, Enrique Saez, Robert S Ross, Aaron P Russell, Anastasia Kralli
OBJECTIVE: Endurance exercise training remodels skeletal muscle, leading to increased mitochondrial content and oxidative capacity. How exercise entrains skeletal muscle signaling pathways to induce adaptive responses remains unclear. In past studies, we identified Perm1 (PGC-1 and ERR induced regulator, muscle 1) as an exercise-induced gene and showed that Perm1 overexpression elicits similar muscle adaptations as endurance exercise training. The mechanism of action and the role of Perm1 in exercise-induced responses are not known...
February 27, 2019: Molecular Metabolism
Giuliana D Noratto, Kevin Murphy, Boon P Chew
The purpose of this study was to investigate if quinoa (Chenopodium quinoa Willd.), a good source of nutrients, fibre, and phytochemicals, can modulate risk disease biomarkers on obese-diabetic (db/db) mice. The db/db mice fed quinoa-supplemented (quinoa) or AIN-93G diet (obese) were compared to lean control fed AIN-93G diet. Quinoa intake reduced at significant level plasma total-cholesterol (total-c), LDL-c, and oxidized-LDL to levels similar to lean; lessened protein carbonyls and interleukin (IL)-6. The hepatic steatosis and total-c accumulation in liver were also similar between lean and quinoa and lower than obese...
July 30, 2019: Food Chemistry
Brandon Boland, Michael B Mumphrey, Zheng Hao, Benji Gill, R Leigh Townsend, Sangho Yu, Heike Münzberg, Christopher D Morrison, James L Trevaskis, Hans-Rudolf Berthoud
BACKGROUND/GOALS: The gut hormone peptide YY (PYY) secreted from intestinal L-cells has been implicated in the mechanisms of satiation via Y2-receptor (Y2R) signaling in the brain and periphery and is a major candidate for mediating the beneficial effects of bariatric surgery on appetite and body weight. METHODS: Here we assessed the role of Y2R signaling in the response to low- and high-fat diets and its role in the effects of Roux-en-Y gastric bypass (RYGB) surgery on body weight, body composition, food intake, energy expenditure and glucose handling, in global Y2R-deficient (Y2RKO) and wildtype (WT) mice made obese on high-fat diet...
March 10, 2019: Nutrients
Rodolphe Dusaulcy, Sandra Handgraaf, Florian Visentin, Cedric Howald, Emmanouil T Dermitzakis, Jacques Philippe, Yvan Gosmain
Characterization of endocrine-cell functions and associated molecular signatures in diabetes is crucial to better understand why and by which mechanisms alpha and beta cells cause and perpetuate metabolic abnormalities. The now recognized role of glucagon in diabetes control is a major incentive to have a better understanding of dysfunctional alpha cells. To characterize molecular alterations of alpha cells in diabetes, we analyzed alpha-cell transcriptome from control and diabetic mice using diet-induced obesity model...
2019: PloS One
Ran Okouchi, Yuto Sakanoi, Tsuyoshi Tsuduki
We investigated whether the difference in miso consumption between the Japanese diets of 1975 and 2010 has influenced the observed increase in diet-induced obesity. To recreate the 2010 and 1975 Japanese high-fat diets with the corresponding proportions of miso, freeze-dried miso was added to high-fat mouse feed at 1.6% and 2.6%, respectively. When 5-week-old male Institute of Cancer Research (ICR) mice were provided each of these diets ad libitum for 8 weeks, it was found that the white adipose tissue weight and adipocyte area were lower in mice receiving the 1975 diet than in those receiving the 2010 diet...
March 6, 2019: Nutrients
Chikako Shimizu, Yoshihisa Wakita, Takashi Inoue, Masanori Hiramitsu, Miki Okada, Yutaka Mitani, Shuichi Segawa, Youichi Tsuchiya, Toshitaka Nabeshima
Polyphenols have been examined for their beneficial effects on health, particularly in rodents, but their lifelong effects are unclear. Lemons (Citrus limon), containing lemon polyphenols (LPP), are widely consumed but the effects of LPP on aging are unknown. Therefore, we examined the effects of LPP on aging such as aging-related scores, locomotor activity, cognitive functions, and intestinal microbiome using senescence-accelerated mouse prone 1 (SAMP1) and senescence-accelerated resistant mouse 1 (SAMR1)...
March 6, 2019: Scientific Reports
Francois Brial, Aurélie Le Lay, Lyamine Hedjazi, Tsz Tsang, Jane F Fearnside, Georg W Otto, Fawaz Alzaid, Steven P Wilder, Nicolas Venteclef, Jean-Baptiste Cazier, Jeremy K Nicholson, Chris Day, Alastair D Burt, Ivo G Gut, Mark Lathrop, Marc-Emmanuel Dumas, Dominique Gauguier
Non-alcoholic fatty liver disease (NAFLD) is often associated with obesity and type 2 diabetes. To disentangle etiological relationships between these conditions and identify genetically-determined metabolites involved in NAFLD processes, we mapped 1 H nuclear magnetic resonance (NMR) metabolomic and disease-related phenotypes in a mouse F2 cross derived from strains showing resistance (BALB/c) and increased susceptibility (129S6) to these diseases. Quantitative trait locus (QTL) analysis based on single nucleotide polymorphism (SNP) genotypes identified diet responsive QTLs in F2 mice fed control or high fat diet (HFD)...
March 6, 2019: Scientific Reports
Scott M Gordon, Edward B Neufeld, Zhihong Yang, Milton Pryor, Lita A Freeman, Xiao Fan, Iftikhar J Kullo, Leslie G Biesecker, Alan T Remaley
Regulation of lipid absorption by enterocytes can influence metabolic status in humans and contribute to obesity and related complications. The intracellular steps of chylomicron biogenesis and transport from the Endoplasmic Reticulum (ER) to the Golgi complex have been described, but the mechanisms for post-Golgi transport and secretion of chylomicrons have not been identified. Using a newly generated Dennd5b-/- mouse, we demonstrate an essential role for this gene in Golgi to plasma membrane transport of chylomicron secretory vesicles...
March 5, 2019: Scientific Reports
Haixia Xu, Xiao Du, Geng Liu, Shuang Huang, Wenya Du, Sailan Zou, Dongmei Tang, Chen Fan, Yongmei Xie, Yuquan Wei, Yan Tian, Xianghui Fu
OBJECTIVE: The mixed lineage kinase domain like (MLKL) protein, receptor interacting protein (RIPK) 1, and RIPK3 are key regulators of necroptosis, a highly pro-inflammatory mode of cell death that has been implicated in various pathological processes and human diseases. However, the role of these necroptotic regulators in diabetes remains unknown. Here we sought to delineate the role of MLKL in insulin resistance and type 2 diabetes (T2D). METHODS: We first analyzed the expression of key necroptotic regulators in obese/diabetic mouse models...
February 20, 2019: Molecular Metabolism
Kripa Shankar, Durgesh Kumar, Sanchita Gupta, Salil Varshney, Sujith Rajan, Ankita Srivastava, Abhishek Gupta, Anand Prakash Gupta, Achchhe Lal Vishwakarma, Jiaur R Gayen, Anil Nilkanth Gaikwad
Obesity results in the chronic activation of innate immune system and subsequently sets in diabetes. Aim of the study was to investigate the immunometabolic role of brown adipose tissue (BAT) in the obesity. We performed both BAT transplantation as well as extirpation experiments in the mouse model of high-fat diet (HFD)-induced obesity. We carried out immune cell profiling in the stromal vascular fraction (SVF) isolated from epididymal white adipose tissue (eWAT). BAT transplantation reversed HFD-induced increase in body weight gain and insulin resistance without altering diet intake...
February 26, 2019: European Journal of Pharmacology
Youngmi Jung, Inyoung Kim, Mohamed Mannaa, Jinnyun Kim, Sihyung Wang, Inmyoung Park, Jieun Kim, Young-Su Seo
Non-alcoholic fatty liver disease (NAFLD) is one of the most common liver disorders. Possible links have been recently found between the gut-microbiota and the host metabolism in development of NAFLD and obesity. Therefore, understanding the changes in intestinal microbiota during the progression of NAFLD, is important. In this study, the effect of Kombucha tea (KT), obtained by microbial fermentation of sugared black tea, was investigated on gut-microbiota during the progression of NAFLD. The results indicated a decrease in Erysipelotrichia class by treatment with KT in comparison to the methionine/choline-deficient (MCD)-fed db/db mice...
February 2019: Food Science and Biotechnology
Noa Corem, Shira Anzi, Sivan Gelb, Ayal Ben-Zvi
Diabetes mellitus (DM) significantly increases susceptibility to central nervous system (CNS) pathologies, including stroke, vascular dementia, cognitive deficits and Alzheimer's disease. Previous studies (mostly using the streptozotocin model) suggested that blood-brain barrier (BBB) disruption is involved in these conditions. Here, we examined the integrity of brain capillaries and BBB permeability in Leprdb/db obesity-related diabetic mice. Surprisingly, significant BBB leakage was observed only in young mice at the pre-hyperglycemic stage...
February 27, 2019: Scientific Reports
Mizuho Sato, Tatsuhiko Goto, Eiichi Inoue, Yuji Miyaguchi, Atsushi Toyoda
Citrus fruits have several potential benefits for maintaining our health. In this study, we investigated the anti-obesity effects of immature Citrus tumida hort. ex Tanaka (C. tumida) peels using an acute obesity mice model. C57BL/6J male mice were divided into 2 groups; HFD-LL subjected to a high fat diet (HFD) and constant light exposure (LL), and HFDC-LL subjected to a HFD containing immature peel powder of C. tumida (5% w/w) and LL. Dietary ingestion of immature C. tumida peels significantly suppressed body weight gain following decreased epidydimal, perirenal, and subcutaneous fat weights...
2019: Journal of Nutritional Science and Vitaminology
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