Muscle-specific TGR5 overexpression improves glucose clearance in glucose-intolerant mice

TGR5, a G protein-coupled bile acid receptor, is expressed in various tissues and regulates several physiological processes. In the skeletal muscle, TGR5 activation is known to induce muscle hypertrophy; however, the effects on glucose and lipid metabolism are not well understood, despite the fact that the skeletal muscle plays a major role in energy metabolism. Here, we demonstrate that skeletal muscle-specific TGR5 transgenic (Tg) mice exhibit increased glucose utilization, without altering the expression of major genes related to glucose and lipid metabolism. Metabolite profiling analysis by CE-TOF MS showed that glycolytic flux was activated in the skeletal muscle of Tg mice, leading to an increase in glucose utilization. Upon long-term, high-fat diet (HFD) challenge, blood glucose clearance was improved in Tg mice without an accompanying increase in insulin sensitivity in skeletal muscle and a reduction of body weight. Moreover, Tg mice showed improved age-associated glucose intolerance. These results strongly suggest that TGR5 ameliorated glucose metabolism disorder that is caused by diet-induced obesity and aging by enhancing the glucose metabolic capacity of skeletal muscle. Our study demonstrates that TGR5 activation in the skeletal muscle is effective in improving glucose metabolism and may be beneficial in developing a novel strategy for the prevention or treatment of hyperglycemia.

Download Full-text

1878-P: The Role and Potential Mechanism of LncRNA Gm15441 in Skeletal Muscle Glucose and Lipid Metabolism

Diabetes ◽

10.2337/db20-1878-p ◽

2020 ◽

Vol 69 (Supplement 1) ◽

pp. 1878-P

Author(s):

LIANGHUI YOU ◽

YU ZENG ◽

NAN GU ◽

CHENBO JI

Keyword(s):

Skeletal Muscle ◽

Lipid Metabolism ◽

Potential Mechanism ◽

Glucose And Lipid Metabolism

Download Full-text

Chlorpyrifos exposure induces lipid metabolism disorder at the physiological and transcriptomic levels in larval zebrafish

Acta Biochimica et Biophysica Sinica ◽

10.1093/abbs/gmz074 ◽

2019 ◽

Vol 51 (9) ◽

pp. 890-899

Author(s):

Xiaoyu Wang ◽

Jiajie Zhou ◽

Manlu Shen ◽

Jiayan Shen ◽

Xinyue Zhang ◽

...

Keyword(s):

Lipid Metabolism ◽

Acid Synthesis ◽

Treated Group ◽

Heart Tissue ◽

Lipid Metabolism Disorder ◽

Larval Zebrafish ◽

Metabolism Disorder ◽

Glucose And Lipid Metabolism ◽

Lipid Metabolism Disorders ◽

Cellular Apoptosis

Abstract Chlorpyrifos (CPF) is a widely used insecticide in pest control, and it can affect aquatic animals by contaminating the water. In this study, larval zebrafish were exposed to CPF at concentrations of 30, 100 and 300 μg/l for 7 days. In the CPF-treated group, lipid droplet accumulation was reduced in larval zebrafish. The levels of triglyceride (TG), total cholesterol (TC), and pyruvate were also decreased after CPF exposure. Cellular apoptosis were significantly increased in the heart tissue after CPF exposure compared with the control. Transcription changes in cardiovascular genes were also observed. Through transcriptome analysis, we found that the transcription of 465 genes changed significantly, with 398 upregulated and 67 downregulated in the CPF-treated group, indicating that CPF exposure altered the transcription of genes. Among these altered genes, a number of genes were closely related to the glucose and lipid metabolism pathways. Furthermore, we also confirmed that the transcription of genes related to fatty acid synthesis, TC synthesis, and lipogenesis were significantly decreased in larval zebrafish after exposure to CPF. These results indicated that CPF exposure induced lipid metabolism disorders associated with cardiovascular toxicity in larval zebrafish.

Download Full-text

Sudachitin, a polymethoxylated flavone, improves glucose and lipid metabolism by increasing mitochondrial biogenesis in skeletal muscle

Nutrition & Metabolism ◽

10.1186/1743-7075-11-32 ◽

2014 ◽

Vol 11 (1) ◽

pp. 32 ◽

Cited By ~ 30

Author(s):

Rie Tsutsumi ◽

Tomomi Yoshida ◽

Yoshitaka Nii ◽

Naoki Okahisa ◽

Shinya Iwata ◽

...

Keyword(s):

Skeletal Muscle ◽

Lipid Metabolism ◽

Mitochondrial Biogenesis ◽

Glucose And Lipid Metabolism

Download Full-text

The Liver as an Endocrine Organ—Linking NAFLD and Insulin Resistance

Endocrine Reviews ◽

10.1210/er.2019-00034 ◽

2019 ◽

Vol 40 (5) ◽

pp. 1367-1393 ◽

Cited By ~ 33

Author(s):

Matthew J Watt ◽

Paula M Miotto ◽

William De Nardo ◽

Magdalene K Montgomery

Keyword(s):

Insulin Resistance ◽

Lipid Metabolism ◽

Liver Disorder ◽

The Body ◽

Limited Information ◽

Peripheral Tissues ◽

Nonalcoholic Fatty Liver ◽

Induce Insulin Resistance ◽

Glucose And Lipid Metabolism ◽

Physiological Processes

AbstractThe liver is a dynamic organ that plays critical roles in many physiological processes, including the regulation of systemic glucose and lipid metabolism. Dysfunctional hepatic lipid metabolism is a cause of nonalcoholic fatty liver disease (NAFLD), the most common chronic liver disorder worldwide, and is closely associated with insulin resistance and type 2 diabetes. Through the use of advanced mass spectrometry “omics” approaches and detailed experimentation in cells, mice, and humans, we now understand that the liver secretes a wide array of proteins, metabolites, and noncoding RNAs (miRNAs) and that many of these secreted factors exert powerful effects on metabolic processes both in the liver and in peripheral tissues. In this review, we summarize the rapidly evolving field of “hepatokine” biology with a particular focus on delineating previously unappreciated communication between the liver and other tissues in the body. We describe the NAFLD-induced changes in secretion of liver proteins, lipids, other metabolites, and miRNAs, and how these molecules alter metabolism in liver, muscle, adipose tissue, and pancreas to induce insulin resistance. We also synthesize the limited information that indicates that extracellular vesicles, and in particular exosomes, may be an important mechanism for intertissue communication in normal physiology and in promoting metabolic dysregulation in NAFLD.

Download Full-text

Quercetin Improves Glucose and Lipid Metabolism of Diabetic Rats: Involvement of Akt Signaling and SIRT1

Journal of Diabetes Research ◽

10.1155/2017/3417306 ◽

2017 ◽

Vol 2017 ◽

pp. 1-10 ◽

Cited By ~ 28

Author(s):

Jing Peng ◽

Qingde Li ◽

Keye Li ◽

Li Zhu ◽

Xiaoding Lin ◽

...

Keyword(s):

Diabetes Mellitus ◽

Lipid Metabolism ◽

Fasting Blood Glucose ◽

Akt Signaling ◽

Hepatic Glycogen ◽

High Dose ◽

Lipid Metabolism Disorder ◽

Metabolism Disorder ◽

Glucose And Lipid Metabolism ◽

Quercetin Treatment

Glucose and lipid metabolism disorder in diabetes mellitus often causes damage to multiple tissues and organs. Diabetes mellitus is beneficially affected by quercetin. However, its concrete mechanisms are yet to be fully elucidated. In our study, diabetes was induced in Sprague-Dawley rats by STZ injection. The rats were randomly divided into normal control, diabetic model, low-dose quercetin treatment, high-dose quercetin treatment, and pioglitazone treatment groups. Fasting blood glucose was collected to evaluate diabetes. Immunohistochemistry and fluorometric assay were performed to explore SIRT1. Akt levels were measured through immunoprecipitation and Western blot. After 12 weeks of quercetin treatment, the biochemical parameters of glucose and lipid metabolism improved to varying degrees. Hepatic histomorphological injury was alleviated, and hepatic glycogen content was increased. The expression and activity of hepatic SIRT1 were enhanced, and Akt was activated by phosphorylation and deacetylation. These results suggested that the beneficial effects of quercetin on glucose and lipid metabolism disorder are probably associated with the upregulated activity and protein level of SIRT1 and its influence on Akt signaling pathway. Hence, quercetin shows potential for the treatment of glucose and lipid metabolism disorder in diabetes mellitus.

Download Full-text

siRNA-based gene silencing reveals specialized roles of IRS-1/Akt2 and IRS-2/Akt1 in glucose and lipid metabolism in human skeletal muscle

Cell Metabolism ◽

10.1016/j.cmet.2006.04.008 ◽

2006 ◽

Vol 4 (1) ◽

pp. 89-96 ◽

Cited By ~ 132

Author(s):

Karim Bouzakri ◽

Anna Zachrisson ◽

Lubna Al-Khalili ◽

Bei B. Zhang ◽

Heikki A. Koistinen ◽

...

Keyword(s):

Skeletal Muscle ◽

Lipid Metabolism ◽

Gene Silencing ◽

Human Skeletal Muscle ◽

Glucose And Lipid Metabolism

Download Full-text

Effects of blockade of fatty acid oxidation on whole body and tissue-specific glucose metabolism in rats

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1993.265.4.e592 ◽

1993 ◽

Vol 265 (4) ◽

pp. E592-E600 ◽

Cited By ~ 4

Author(s):

A. B. Jenkins ◽

L. H. Storlien ◽

G. J. Cooney ◽

G. S. Denyer ◽

I. D. Caterson ◽

...

Keyword(s):

Skeletal Muscle ◽

Fatty Acid ◽

Glucose Metabolism ◽

Fatty Acid Oxidation ◽

Pyruvate Dehydrogenase ◽

Glucose Utilization ◽

Whole Body ◽

Acid Oxidation ◽

Tissue Specific ◽

Glucose Output

We examined the effect of the long-chain fatty acid oxidation blocker methyl palmoxirate (methyl 2-tetradecyloxiranecarboxylate, McN-3716) on glucose metabolism in conscious rats. Fasted animals [5 h with or without hyperinsulinemia (100 mU/l) and 24 h] received methyl palmoxirate (30 or 100 mg/kg body wt po) or vehicle 30 min before a euglycemic glucose clamp. Whole body and tissue-specific glucose metabolism were calculated from 2-deoxy-[3H]-glucose kinetics and accumulation. Oxidative metabolism was assessed by respiratory gas exchange in 24-h fasted animals. Pyruvate dehydrogenase complex activation was determined in selected tissues. Methyl palmoxirate suppressed whole body lipid oxidation by 40-50% in 24-h fasted animals, whereas carbohydrate oxidation was stimulated 8- to 10-fold. Whole body glucose utilization was not significantly affected by methyl palmoxirate under any conditions; hepatic glucose output was suppressed only in the predominantly gluconeogenic 24-h fasted animals. Methyl palmoxirate stimulated glucose uptake in heart in 24-h fasted animals [15 +/- 5 vs. 220 +/- 28 (SE) mumol x 100 g-1 x min-1], with smaller effects in 5-h fasted animals with or without hyperinsulinemia. Methyl palmoxirate induced significant activation of pyruvate dehydrogenase in heart in the basal state, but not during hyperinsulinemia. In skeletal muscles, methyl palmoxirate suppressed glucose utilization in the basal state but had no effect during hyperinsulinemia; pyruvate dehydrogenase activation in skeletal muscle was not affected by methyl palmoxirate under any conditions. The responses in skeletal muscle are consistent with the operation of a mechanism similar to the Pasteur effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Download Full-text