Transient Receptor Potential Canonical Channel‐1 (TRPC1) KO Mice That Exercise Are Protected from High‐Fat Diet‐induced Obesity and Type 2 Diabetes Risk

Background: As of 2018, 2.1 billion people nearly 30% of the world’s population are either obese or overweight. Worldwide obesity has nearly tripled since 1975. It is an emerging health problem with major adverse effects on health. It is a risk factor for many chronic diseases but is best known for its role in metabolic syndrome, which can lead to type 2 diabetes mellitus as well as cardiovascular diseases. Anti-obesity drugs are available but have many side effects. Voglibose, an antidiabetic drug, is an alpha glucosidase inhibitor which shows promising results in the reduction of body weight with minimal side effects.Methods: Voglibose (7 mg/kg) was administered to rats fed with normal laboratory chows and high fat diet to see its effect on body weight, body mass index, abdominal and thoracic circumference, and lipid profile at the end of 12 weeks.Results: Administration of voglibose significantly reduced food consumption, feed efficiency and increase in body weight induced by high fat diet in rats. Rats fed on normal diet also showed reductions in the same parameters, suggesting its weight lowering effect. Reductions in the anthropometric measurements, hypolipidemic effects and glucose lowering effects were also observed.Conclusions: Voglibose prevented high fat diet-induced obesity and improvement in metabolic profile, which ultimately has systemic effects on body weight in rats. Further studies are needed to see its potential therapeutic use in obese patients with type 2 diabetes mellitus, and related complications.

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Common genetic variants of the ion channel transient receptor potential membrane melastatin 6 and 7 (TRPM6 and TRPM7), magnesium intake, and risk of type 2 diabetes in women

BMC Medical Genetics ◽

10.1186/1471-2350-10-4 ◽

2009 ◽

Vol 10 (1) ◽

Cited By ~ 51

Author(s):

Yiqing Song ◽

Yi-Hsiang Hsu ◽

Tianhua Niu ◽

JoAnn E Manson ◽

Julie E Buring ◽

...

Keyword(s):

Type 2 Diabetes ◽

Ion Channel ◽

Genetic Variants ◽

Transient Receptor Potential ◽

Receptor Potential ◽

Magnesium Intake ◽

Common Genetic Variants ◽

Transient Receptor

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Paternal exercise protects mouse offspring from high-fat-diet-induced type 2 diabetes risk by increasing skeletal muscle insulin signaling

The Journal of Nutritional Biochemistry ◽

10.1016/j.jnutbio.2018.03.013 ◽

2018 ◽

Vol 57 ◽

pp. 35-44 ◽

Cited By ~ 7

Author(s):

Danielle Krout ◽

James N. Roemmich ◽

Amy Bundy ◽

Rolando A. Garcia ◽

Lin Yan ◽

...

Keyword(s):

Type 2 Diabetes ◽

Skeletal Muscle ◽

Insulin Signaling ◽

High Fat Diet ◽

Diabetes Risk ◽

High Fat

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RGC32 deficiency protects against high-fat diet-induced obesity and insulin resistance in mice

Journal of Endocrinology ◽

10.1530/joe-14-0548 ◽

2014 ◽

Vol 224 (2) ◽

pp. 127-137 ◽

Cited By ~ 21

Author(s):

Xiao-Bing Cui ◽

Jun-Na Luan ◽

Jianping Ye ◽

Shi-You Chen

Keyword(s):

Insulin Resistance ◽

Type 2 Diabetes ◽

Adipose Tissue ◽

High Fat Diet ◽

Tolerance Test ◽

High Fat ◽

Diet Induced Obesity

Obesity is an important independent risk factor for type 2 diabetes, cardiovascular diseases and many other chronic diseases. Adipose tissue inflammation is a critical link between obesity and insulin resistance and type 2 diabetes and a contributor to disease susceptibility and progression. The objective of this study was to determine the role of response gene to complement 32 (RGC32) in the development of obesity and insulin resistance. WT and RGC32 knockout (Rgc32−/− (Rgcc)) mice were fed normal chow or high-fat diet (HFD) for 12 weeks. Metabolic, biochemical, and histologic analyses were performed. 3T3-L1 preadipocytes were used to study the role of RGC32 in adipocytes in vitro. Rgc32−/− mice fed with HFD exhibited a lean phenotype with reduced epididymal fat weight compared with WT controls. Blood biochemical analysis and insulin tolerance test showed that RGC32 deficiency improved HFD-induced dyslipidemia and insulin resistance. Although it had no effect on adipocyte differentiation, RGC32 deficiency ameliorated adipose tissue and systemic inflammation. Moreover, Rgc32−/− induced browning of adipose tissues and increased energy expenditure. Our data indicated that RGC32 plays an important role in diet-induced obesity and insulin resistance, and thus it may serve as a potential novel drug target for developing therapeutics to treat obesity and metabolic disorders.

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A Comparative Study of the Metabolic and Skeletal Response of C57BL/6J and C57BL/6N Mice in a Diet-Induced Model of Type 2 Diabetes

Journal of Nutrition and Metabolism ◽

10.1155/2015/758080 ◽

2015 ◽

Vol 2015 ◽

pp. 1-13 ◽

Cited By ~ 19

Author(s):

Elizabeth Rendina-Ruedy ◽

Kelsey D. Hembree ◽

Angela Sasaki ◽

McKale R. Davis ◽

Stan A. Lightfoot ◽

...

Keyword(s):

Type 2 Diabetes ◽

High Fat Diet ◽

Plasma Insulin ◽

Data Interpretation ◽

Negative Control ◽

High Fat ◽

Diet Induced Obesity ◽

Altered Glucose

Type 2 diabetes mellitus (T2DM) represents a complex clinical scenario of altered energy metabolism and increased fracture incidence. The C57BL/6 mouse model of diet-induced obesity has been used to study the mechanisms by which altered glucose homeostasis affects bone mass and quality, but genetic variations in substrains of C57BL/6 may have confounded data interpretation. This study investigated the long-term metabolic and skeletal consequences of two commonly used C57BL/6 substrains to a high fat (HF) diet. Male C57BL/6J, C57BL/6N, and the negative control strain, C3H/HeJ, mice were fed a control or HF diet for 24 wks. C57BL/6N mice on a HF diet demonstrated an increase in plasma insulin and blood glucose as early as 4 wk, whereas these responses were delayed in the C57BL/6J mice. The C57BL/6N mice exhibited more severe hepatic steatosis and inflammation. Only the C57BL/6N mice lost significant trabecular bone in response to the high fat diet. The C3H/HeJ mice were protected from bone loss. The data show that C57BL/6J and C57BL/6N mice differ in their metabolic and skeletal response when fed a HF diet. These substrain differences should be considered when designing experiments and are likely to have implications on data interpretation and reproducibility.

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Abstract 419: Metabocin TM Increases Lipolytic Pathways to Counter High Fat Diet-Induced Non-Alcoholic Fatty Liver Disease

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/atvb.36.suppl_1.419 ◽

2016 ◽

Vol 36 (suppl_1) ◽

Author(s):

Baskaran Thyagarajan ◽

Sara Cisneros ◽

Ross Cook ◽

Padmamalini Baskaran

Keyword(s):

High Fat Diet ◽

Transient Receptor Potential ◽

Receptor Potential ◽

Sirtuin 1 ◽

Transient Receptor Potential Vanilloid ◽

High Fat ◽

Ppar Alpha ◽

Alcoholic Fatty Liver ◽

Transient Receptor ◽

Alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFDLD) is a comorbidity of high fat diet-induced obesity. NAFLD leads to steatohepatitis and hepatic steatosis, which progress into cirrhosis and liver cancer. Currently, there is no single strategy to counter NAFLD. In our effort to understand the role of transient receptor potential vanilloid receptor in the pathophysiology of high fat diet-induced, non-alcoholic fatty liver disease, we discovered that mammalian liver expresses transient receptor potential vanilloid 1 protein and that Metabocin TM {( E )- N -[(4-hydroxy-3-methoxyphenyl) methyl]-8-methylnon-6-enamide; also know as capsaicin; an agonist of transient receptor potential vanilloid 1 channel protein} significantly prevented mice from diet-induced NAFLD. Feeding high fat diet (60% calories from fat) for 32 weeks, from the age of 6 weeks until 38 weeks, caused hypertension, hyperglycemia, glucose intolerance and hyper triglyceridemia in the wild type mice and Metabocin TM prevented these effects. Metabocin TM markedly prevented hepatic steatosis and decreased lipid accumulation in the liver. Also, Metabocin TM significantly increased the expression of lipolytic PPAR alpha, PPAR gamma co activator 1 alpha, sirtuin-1 and forkhead box protein 01, while suppressed the expression of lipogenic stearoyl CoA desaturase 1. Further, Metabocin TM increased liver lipolysis, facilitated the activation of sirtuin-1 via Ca 2+ /Calmodulin dependent protein kinase II/AMPK-dependent mechanism and induced an interaction between sirtuin-1 and PPAR alpha. Metabocin TM also increased the expression of lipin-1 (a transcriptional regulator of PPAR alpha) and mitochondrial UCP-1. Our data provide evidence for the emergence of Metabocin TM as a novel drug molecule to antagonize NAFLD and its associated pathologies.

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1'-Acetoxychavicol acetate, a potent transient receptor potential ankyrin 1 agonist derived from Thai ginger, prevents visceral fat accumulation in mice fed a high-fat and high-sucrose diet

Bioscience Biotechnology and Biochemistry ◽

10.1093/bbb/zbab131 ◽

2021 ◽

Author(s):

Tatsunori Ikeya ◽

Yuko Terada ◽

Yasujiro Morimitsu ◽

Kikue Kubota ◽

Keisuke Ito ◽

...

Keyword(s):

Transient Receptor Potential ◽

Receptor Potential ◽

High Fat ◽

Visceral Fat Accumulation ◽

Diet Induced Obesity ◽

Sucrose Diet ◽

High Sucrose Diet ◽

Transient Receptor ◽

Sympathetic Nerve Activation ◽

High Sucrose

Abstract 1'-Acetoxychavicol acetate (ACA) is found in Thai ginger (Alpinia galanga) and is a powerful agonist of transient receptor potential ankyrin 1 (TRPA1). In a diet-induced obesity mouse model, ACA reduced fat deposition. Sympathetic nerve activation was also indicated in the ACA fed group. This study is expected to promote the utilization of food containing TRPA1 agonists to treat obesity.

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