scholarly journals Thrombospondin 1 Mediates High-Fat Diet-Induced Muscle Fibrosis and Insulin Resistance in Male Mice

Endocrinology ◽  
2013 ◽  
Vol 154 (12) ◽  
pp. 4548-4559 ◽  
Author(s):  
Mayumi Inoue ◽  
Yibin Jiang ◽  
Richard H. Barnes ◽  
Masakuni Tokunaga ◽  
Gabriel Martinez-Santibañez ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
High Fat Diet ◽  
Skeletal Muscles ◽  
Matrix Protein ◽  
Extracellular Matrix Protein ◽  
Male Mice ◽  
High Fat ◽  
Adipose Tissues ◽  
Early Stages ◽  
Thrombospondin 1

Thrombospondin 1 (THBS1 or TSP-1) is a circulating glycoprotein highly expressed in hypertrophic visceral adipose tissues of humans and mice. High-fat diet (HFD) feeding induces the robust increase of circulating THBS1 in the early stages of HFD challenge. The loss of Thbs1 protects male mice from diet-induced weight gain and adipocyte hypertrophy. Hyperinsulinemic euglycemic clamp study has demonstrated that Thbs1-null mice are protected from HFD-induced insulin resistance. Tissue-specific glucose uptake study has revealed that the insulin-sensitive phenotype of Thbs1-null mice is mostly mediated by skeletal muscles. Further assessments of the muscle phenotype using RNA sequencing, quantitative PCR, and histological studies have demonstrated that Thbs1-null skeletal muscles are protected from the HFD-dependent induction of Col3a1 and Col6a1, coupled with a new collagen deposition. At the same time, the Thbs1-null mice display a better circadian rhythm and higher amplitude of energy expenditure with a browning phenotype in sc adipose tissues. These results suggest that THBS1, which circulates in response to a HFD, may induce insulin resistance and fibrotic tissue damage in skeletal muscles as well as the de-browning of sc adipose tissues in the early stages of a HFD challenge. Our study may shed new light on the pathogenic role played by a circulating extracellular matrix protein in the cross talk between adipose tissues and skeletal muscles during obesity progression.

scholarly journals GABA Type B Receptor Signaling in Proopiomelanocortin Neurons Protects Against Obesity, Insulin Resistance, and Hypothalamic Inflammation in Male Mice on a High-Fat Diet

2013 ◽  
Vol 33 (43) ◽  
pp. 17166-17173 ◽  
Author(s):  
Yoshihiro Ito ◽  
Ryoichi Banno ◽  
Miyuki Shibata ◽  
Koichi Adachi ◽  
Shigeru Hagimoto ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
High Fat Diet ◽  
Receptor Signaling ◽  
Male Mice ◽  
Type B ◽  
High Fat ◽  
Hypothalamic Inflammation

scholarly journals Metabolic dysfunction in female mice with disruption of 5α-reductase 1

2017 ◽  
Vol 232 (1) ◽  
pp. 29-36 ◽  
Author(s):  
Dawn E W Livingstone ◽  
Emma M Di Rollo ◽  
Tracy C-S Mak ◽  
Karen Sooy ◽  
Brian R Walker ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Hepatic Steatosis ◽  
Stress Responses ◽  
High Fat Diet ◽  
Metabolic Dysfunction ◽  
Male Mice ◽  
High Fat ◽  
Female Mice ◽  
Normal Chow ◽  
Transcript Profiles

5α-Reductases irreversibly catalyse A-ring reduction of pregnene steroids, including glucocorticoids and androgens. Genetic disruption of 5α-reductase 1 in male mice impairs glucocorticoid clearance and predisposes to glucose intolerance and hepatic steatosis upon metabolic challenge. However, it is unclear whether this is driven by changes in androgen and/or glucocorticoid action. Female mice with transgenic disruption of 5α-reductase 1 (5αR1-KO) were studied, representing a ‘low androgen’ state. Glucocorticoid clearance and stress responses were studied in mice aged 6 months. Metabolism was assessed in mice on normal chow (aged 6 and 12 m) and also in a separate cohort following 1-month high-fat diet (aged 3 m). Female 5αR1-KO mice had adrenal suppression (44% lower AUC corticosterone after stress), and upon corticosterone infusion, accumulated hepatic glucocorticoids (~27% increased corticosterone). Female 5αR1-KO mice aged 6 m fed normal chow demonstrated insulin resistance (~35% increased area under curve (AUC) for insulin upon glucose tolerance testing) and hepatic steatosis (~33% increased hepatic triglycerides) compared with controls. This progressed to obesity (~12% increased body weight) and sustained insulin resistance (~38% increased AUC insulin) by age 12 m. Hepatic transcript profiles supported impaired lipid β-oxidation and increased triglyceride storage. Female 5αR1-KO mice were also predisposed to develop high-fat diet-induced insulin resistance. Exaggerated predisposition to metabolic disorders in female mice, compared with that seen in male mice, after disruption of 5αR1 suggests phenotypic changes may be underpinned by altered metabolism of glucocorticoids rather than androgens.

scholarly journals High-fat diet leads to key hepatic miRNAs modulation that may drive lipid accumulation in liver that preceds insulin resistance in male mice

2018 ◽  
Author(s):  
Carolina Panzarin ◽  
Adriana Souza Torsoni ◽  
Laís A. de P. Simino ◽  
Mariana C. S. Mancini ◽  
Marina F. Fontana ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Liver Disease ◽  
Lipid Accumulation ◽  
High Fat Diet ◽  
Fatty Liver Disease ◽  
Male Mice ◽  
High Fat ◽  
Alcoholic Fatty Liver ◽  
Prevalence Of Obesity ◽  
Alcoholic Fatty Liver Disease

High-fat diet (HFD) consumption can lead to Non-Alcoholic Fatty Liver Disease (NAFLD), which is characterized by hepatic triglycerides accumulation and is directly associated with the prevalence of obesity in worldwide. Insulin resistance underlies the genesis of both obesity and NAFLD. These mecanisms can be regulated by microRNAs, such as miR-122 and Let-7 in the liver. Therefore, the aim of the present study was to investigate a possible connection between insulin resistance, obesity, NAFLD development and alterations in miR-122 and Let-7 expression in mice fed a HFD.

scholarly journals Insulin resistance without elevated mammalian target of rapamycin complex 1 activity in muscles of mice fed a high-fat diet

2009 ◽  
Vol 107 (5) ◽  
pp. 1479-1485 ◽  
Author(s):  
Thomas H. Reynolds ◽  
Nicholas Cinquino ◽  
Marcus Anthony ◽  
Charles B. Phelps ◽  
E. Zachary Berk
Keyword(s):  
Insulin Resistance ◽  
High Fat Diet ◽  
Skeletal Muscles ◽  
Insulin Action ◽  
Mammalian Target Of Rapamycin ◽  
Specific Inhibitor ◽  
Target Of Rapamycin ◽  
High Fat ◽  
Mtorc1 Signaling

The mammalian target of rapamycin complex 1 (mTORC1) appears to mediate the development of insulin resistance in cultured cells. We studied in vivo insulin action and mTORC1 signaling in skeletal muscles of mice fed a normal chow [control (CON)] diet or a high-fat diet (HFD) for 16 wk. We assessed in vivo insulin action by measuring glucose tolerance (GT), insulin tolerance (IT), and insulin-assisted GT (IAGT). Although GT was not altered, the HFD significantly reduced IT and IAGT. Acute treatment with rapamycin, a highly specific inhibitor of mTORC1, did not improve GT, IT, or IAGT in mice fed the CON diet or the HFD. Phosphorylation of S6 kinase (S6K) on Thr389, a surrogate measure of mTORC1 kinase activity, was assessed in skeletal muscles of mice 15 min after an intraperitoneal injection of insulin or saline. In the basal state and after insulin stimulation, phosphorylation of S6K on Thr389 was similar in muscles of mice fed the HFD and mice fed the CON diet, indicating that mTORC1 activity is not elevated. Furthermore, phosphorylation of insulin receptor substrate 1 on Ser636, a site phosphorylated by mTORC1, was similar in muscles of mice fed the HFD and mice fed the CON diet. Taken together, these findings indicate that in vivo insulin resistance can occur without an increase in mTORC1 activity in skeletal muscle and that inhibition of mTORC1 with rapamycin does not improve insulin action.

scholarly journals Effects of β-glucan Rich Barley Flour on Glucose and Lipid Metabolism in the Ileum, Liver, and Adipose Tissues of High-Fat Diet Induced-Obesity Model Male Mice Analyzed by DNA Microarray

Nutrients ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3546
Author(s):  
Kento Mio ◽  
Chiemi Yamanaka ◽  
Tsubasa Matsuoka ◽  
Toshiki Kobayashi ◽  
Seiichiro Aoe
Keyword(s):  
Lipid Metabolism ◽  
Dna Microarray ◽  
High Fat Diet ◽  
Male Mice ◽  
High Fat ◽  
Barley Flour ◽  
Adipose Tissues ◽  
Expression Levels ◽  
Glucose And Lipid Metabolism ◽  
Expression Of Genes

We evaluated whether intake of β-glucan-rich barley flour affects expression levels of genes related to glucose and lipid metabolism in the ileum, liver, and adipose tissues of mice fed a high-fat diet. C57BL/6J male mice were fed a high-fat diet supplemented with high β-glucan barley, for 92 days. We measured the expression levels of genes involved in glucose and lipid metabolism in the ileum, liver, and adipose tissues using DNA microarray and q-PCR. The concentration of short-chain fatty acids (SCFAs) in the cecum was analyzed by GC/MS. The metabolic syndrome indices were improved by barley flour intake. Microarray analysis showed that the expression of genes related to steroid synthesis was consistently decreased in the liver and adipose tissues. The expression of genes involved in glucose metabolism did not change in these organs. In liver, a negative correlation was showed between some SCFAs and the expression levels of mRNA related to lipid synthesis and degradation. Barley flour affects lipid metabolism at the gene expression levels in both liver and adipose tissues. We suggest that SCFAs are associated with changes in the expression levels of genes related to lipid metabolism in the liver and adipose tissues, which affect lipid accumulation.

scholarly journals Assisted Reproductive Technologies Predispose to Insulin Resistance and Obesity in Male Mice Challenged With a High-Fat Diet

Endocrinology ◽  
2017 ◽  
Vol 158 (5) ◽  
pp. 1152-1159 ◽  
Author(s):  
David Cerny ◽  
Claudio Sartori ◽  
Stefano F. Rimoldi ◽  
Théo Meister ◽  
Rodrigo Soria ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
High Fat Diet ◽  
Assisted Reproductive Technologies ◽  
Reproductive Technologies ◽  
Male Mice ◽  
High Fat

scholarly journals Inhibition of CeramideDe NovoSynthesis Ameliorates Diet Induced Skeletal Muscles Insulin Resistance

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Krzysztof Kurek ◽  
Agnieszka Mikłosz ◽  
Bartłomiej Łukaszuk ◽  
Adrian Chabowski ◽  
Jan Górski ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
High Fat Diet ◽  
Skeletal Muscles ◽  
De Novo ◽  
High Fat ◽  
Ceramide Synthesis ◽  
Sphingosine 1 Phosphate ◽  
The One

Nowadays wrong nutritional habits and lack of physical activity give a rich soil for the development of insulin resistance and obesity. Many researches indicate lipids, especially the one from the sphingolipids class, as the group of molecules heavily implicated in the progress of insulin resistance in skeletal muscle. Recently, scientists have focused their scrutiny on myriocin, a potent chemical compound that inhibits ceramide (i.e., central hub of sphingolipids signaling pathway)de novosynthesis. In the present research we evaluated the effects of myriocin application on type 2 diabetes mellitus in three different types of skeletal muscles: (1) slow-oxidative (red gastrocnemius), (2) oxidative-glycolytic (soleus), and (3) glycolytic (white gastrocnemius). For these reasons the animals were randomly divided into four groups: “control” (C), “myriocin” (M), “high fat diet” (HFD), “high fat diet” (HFD), and “high fat diet + myriocin” (HFD + M). Ourin vivostudy demonstrated that ceramide synthesis inhibition reduces intramuscular ceramide, its precursor sphinganine, and its derivatives sphingosine and sphingosine-1-phosphate concentrations. Moreover, FFA and TG contents were also decreased after myriocin treatment. Thus, myriocin presents potential therapeutic perspectives with respect to the treatment of insulin resistance and its serious consequences in obese patients.

scholarly journals Deletion of PPAR  in adipose tissues of mice protects against high fat diet-induced obesity and insulin resistance

2005 ◽  
Vol 102 (17) ◽  
pp. 6207-6212 ◽  
Author(s):  
J. R. Jones ◽  
C. Barrick ◽  
K.-A. Kim ◽  
J. Lindner ◽  
B. Blondeau ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
High Fat Diet ◽  
High Fat ◽  
Adipose Tissues ◽  
Diet Induced Obesity

scholarly journals Inhibition of PAI-1 attenuates perirenal fat inflammation and the associated nephropathy in high-fat diet-induced obese mice

2019 ◽  
Vol 316 (2) ◽  
pp. E260-E267 ◽  
Author(s):  
Yong Liu ◽  
Lin Wang ◽  
Mao Luo ◽  
Ni Chen ◽  
Xin Deng ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Diabetic Nephropathy ◽  
High Fat Diet ◽  
Matrix Protein ◽  
Macrophage Polarization ◽  
Extracellular Matrix Protein ◽  
Obese Mouse ◽  
High Fat ◽  
Pai 1 ◽  
Perirenal Fat

Plasminogen activator inhibitor-1 (PAI-1) is increasingly recognized as a mediator in extracellular matrix (ECM) accumulation in diabetic nephropathy. Previous studies have implicated PAI-1 in adipose tissue (AT) expansion, while also contributing to insulin resistance. As inflammation is also known to occur in perirenal AT during obesity, we hypothesized that in a high-fat diet (HFD)-induced obese mouse model, PAI-1 contributes to macrophage-mediated inflammation and diabetic nephropathy. The HFD mice showed increased expression of PAI-1 in perirenal fat and also displayed increased fat weight and macrophage numbers. We found that the macrophage polarization, proinflammatory macrophage-M1-phenotype, including CD11c, IL-6, and monocyte chemoattractant protein-1, were increased by an HFD and decreased by either the genetic depletion of PAI-1 or treatment with the PAI-1 inhibitor, PAI-039. Similarly, an enhanced anti-inflammatory M2-phenotype, including CD206 and IL-10, was accompanied by either the genetic deletion of PAI-1 or PAI-039 treatment. Furthermore, the inhibition of PAI-1 reduced HFD-induced renal histological lesions and abated profibrotic/extracellular-matrix protein. Collectively, our findings provide support that PAI-1 contributes to the development of inflammation in perirenal fat and correlates with the development of diabetic nephropathy in HFD-induced obesity.

Sign in / Sign up

Export Citation Format

Share Document