GIP receptor antagonism reverses obesity, insulin resistance, and associated metabolic disturbances induced in mice by prolonged consumption of high-fat diet

2007 ◽  
Vol 293 (6) ◽  
pp. E1746-E1755 ◽  
Author(s):  
Paula L. McClean ◽  
Nigel Irwin ◽  
Roslyn S. Cassidy ◽  
Jens J. Holst ◽  
Victor A. Gault ◽  
...  
Keyword(s):  
High Fat Diet ◽  
Effective Means ◽  
Gastric Inhibitory Polypeptide ◽  
High Fat ◽  
Metabolic Disturbances ◽  
Tissue Mass ◽  
Receptor Antagonism ◽  
Gut Hormone ◽  
Diet Intake ◽  
Gip Receptor

The gut hormone gastric inhibitory polypeptide (GIP) plays a key role in glucose homeostasis and lipid metabolism. This study investigated the effects of administration of a stable and specific GIP receptor antagonist, (Pro3)GIP, in mice previously fed a high-fat diet for 160 days to induce obesity and related diabetes. Daily intraperitoneal injection of (Pro3)GIP over 50 days significantly decreased body weight compared with saline-treated controls, with a modest increase in locomotor activity but no change of high-fat diet intake. Plasma glucose, glycated hemoglobin, and pancreatic insulin were restored to levels of chow-fed mice, and circulating triglyceride and cholesterol were significantly decreased. (Pro3)GIP treatment also significantly decreased circulating glucagon and corticosterone, but concentrations of GLP-1, GIP, resistin, and adiponectin were unchanged. Adipose tissue mass, adipocyte hypertrophy, and deposition of triglyceride in liver and muscle were significantly decreased. These changes were accompanied by significant improvement of insulin sensitivity, meal tolerance, and normalization of glucose tolerance in (Pro3)GIP-treated high-fat-fed mice. (Pro3)GIP concentrations peaked rapidly and remained elevated 24 h after injection. These data indicate that GIP receptor antagonism using (Pro3)GIP provides an effective means of countering obesity and related diabetes induced by consumption of a high-fat, energy-rich diet.

scholarly journals Proto-oncoprotein Zbtb7c and SIRT1 repression: implications in high-fat diet-induced and age-dependent obesity

2021 ◽  
Author(s):  
Won-Il Choi ◽  
Jae-Hyun Yoon ◽  
Seo-Hyun Choi ◽  
Bu-Nam Jeon ◽  
Hail Kim ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
High Fat Diet ◽  
Target Genes ◽  
Proximal Promoter ◽  
High Fat ◽  
Tissue Mass ◽  
Adipose Tissues ◽  
Adipose Tissue Mass ◽  
Age Dependent ◽  
Treatment Of Diabetes

AbstractZbtb7c is a proto-oncoprotein that controls the cell cycle and glucose, glutamate, and lipid metabolism. Zbtb7c expression is increased in the liver and white adipose tissues of aging or high-fat diet-fed mice. Knockout or knockdown of Zbtb7c gene expression inhibits the adipocyte differentiation of 3T3-L1 cells and decreases adipose tissue mass in aging mice. We found that Zbtb7c was a potent transcriptional repressor of SIRT1 and that SIRT1 was derepressed in various tissues of Zbtb7c-KO mice. Mechanistically, Zbtb7c interacted with p53 and bound to the proximal promoter p53RE1 and p53RE2 to repress the SIRT1 gene, in which p53RE2 was particularly critical. Zbtb7c induced p53 to interact with the corepressor mSin3A-HADC1 complex at p53RE. By repressing the SIRT1 gene, Zbtb7c increased the acetylation of Pgc-1α and Pparγ, which resulted in repression or activation of Pgc-1α or Pparγ target genes involved in lipid metabolism. Our study provides a molecular target that can overexpress SIRT1 protein in the liver, pancreas, and adipose tissues, which can be beneficial in the treatment of diabetes, obesity, longevity, etc.

scholarly journals Effect of long-term high-fat diet intake on peripheral insulin sensibility, blood pressure, and renal function in female rats

2016 ◽  
Vol 60 (1) ◽  
pp. 28536 ◽  
Author(s):  
Noemi A. V. Roza ◽  
Luiz F. Possignolo ◽  
Adrianne C. Palanch ◽  
José A. R. Gontijo
Keyword(s):  
Blood Pressure ◽  
Renal Function ◽  
High Fat Diet ◽  
Female Rats ◽  
High Fat ◽  
Diet Intake

scholarly journals High-fat diet intake induces depressive-like behavior in ovariectomized rats

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Valter T. Boldarine ◽  
Amanda P. Pedroso ◽  
Nelson I. P. Neto ◽  
Ana P. S. Dornellas ◽  
Cláudia M. O. Nascimento ◽  
...  
Keyword(s):  
High Fat Diet ◽  
Ovariectomized Rats ◽  
High Fat ◽  
Diet Intake

scholarly journals Short-term high-fat diet intake leads to exacerbation of concanavalin A-induced liver injury through the induction of procoagulation state

2020 ◽  
Vol 22 ◽  
pp. 100736 ◽  
Author(s):  
Eri Nanizawa ◽  
Yuki Tamaki ◽  
Reika Sono ◽  
Rintaro Miyashita ◽  
Yumi Hayashi ◽  
...  
Keyword(s):  
Liver Injury ◽  
Concanavalin A ◽  
High Fat Diet ◽  
High Fat ◽  
Short Term ◽  
Diet Intake

A jaboticaba extract prevents prostatic damage associated with aging and high-fat diet intake

2020 ◽  
Vol 11 (2) ◽  
pp. 1547-1559 ◽  
Author(s):  
C. A. Lamas ◽  
L. A. Kido ◽  
F. Montico ◽  
C. B. Collares-Buzato ◽  
M. R. Maróstica ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
High Fat Diet ◽  
High Fat ◽  
Lesion Development ◽  
Diet Intake

Jaboticaba extract prevented the prostatic lesion development in aging and/or overweight mice, mainly interfering in cell proliferation, hormonal and angiogenesis pathways.

scholarly journals Time-dependent behavioral, neurochemical, and metabolic dysregulation in female C57BL/6 mice caused by chronic high-fat diet intake

2016 ◽  
Vol 157 ◽  
pp. 196-208 ◽  
Author(s):  
Saritha Krishna ◽  
Zhoumeng Lin ◽  
Claire B. de La Serre ◽  
John J. Wagner ◽  
Donald H. Harn ◽  
...  
Keyword(s):  
High Fat Diet ◽  
Time Dependent ◽  
High Fat ◽  
Metabolic Dysregulation ◽  
Diet Intake

scholarly journals Time-course morphological and functional disorders of the kidney induced by long-term high-fat diet intake in female rats

2013 ◽  
Vol 28 (10) ◽  
pp. 2464-2476 ◽  
Author(s):  
C. S. Pinhal ◽  
A. Lopes ◽  
D. B. Torres ◽  
S. L. Felisbino ◽  
J. A. Rocha Gontijo ◽  
...  
Keyword(s):  
High Fat Diet ◽  
Time Course ◽  
Female Rats ◽  
Functional Disorders ◽  
High Fat ◽  
Diet Intake

scholarly journals Morphometric and molecular study of corpus cavernosum of the rat after longterm high-fat diet intake

2009 ◽  
Vol 15 (S3) ◽  
pp. 21-22 ◽  
Author(s):  
I. Tomada ◽  
N. Tomada ◽  
H. Almeida ◽  
P. Vendeira ◽  
D. Neves
Keyword(s):  
Endothelial Dysfunction ◽  
High Fat Diet ◽  
Corpus Cavernosum ◽  
Molecular Study ◽  
High Fat ◽  
Erectile Tissue ◽  
Atherosclerosis Progression ◽  
Regular Consumption ◽  
Diet Intake ◽  
Regular Intake

AbstractErectile dysfunction (ED) is considered equivalent to endothelial dysfunction and thus an early manifestation of atherosclerosis and cardiovascular disease (CVD). Atherosclerosis that is frequently provoked by regular consumption of high-fat diet (HFD) has been recently recognized as a chronic inflammation condition associated to vessel lipid deposition and vascular smooth cells proliferation that together impair endothelium-dependent relaxation of corpus cavernosum (CC) smooth muscle. It is also well established that HFD regular intake by its own induces endothelial dysfunction. The main objective of this study was to evaluate effects of HFD continuous intake on atherosclerosis progression of CC vessels of the rat. Due to their intervention on atherosclerosisrelated vascular remodelling pathways, angiopoietins (Ang1, Ang2) expression in erectile tissue of this rat experimental model was characterized.

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