scholarly journals Muscle-Specific Deletion of Carnitine Acetyltransferase Compromises Glucose Tolerance and Metabolic Flexibility

2012 ◽  
Vol 15 (5) ◽  
pp. 764-777 ◽  
Author(s):  
Deborah M. Muoio ◽  
Robert C. Noland ◽  
Jean-Paul Kovalik ◽  
Sarah E. Seiler ◽  
Michael N. Davies ◽  
...  
Keyword(s):  
Glucose Tolerance ◽  
Metabolic Flexibility ◽  
Carnitine Acetyltransferase ◽  
Specific Deletion

scholarly journals The depot-specific and essential roles of CBP/p300 in regulating adipose plasticity

2019 ◽  
Vol 240 (2) ◽  
pp. 257-269 ◽  
Author(s):  
Maria Namwanje ◽  
Longhua Liu ◽  
Michelle Chan ◽  
Nikki Aaron ◽  
Michael J Kraakman ◽  
...  
Keyword(s):  
Body Weight ◽  
Glucose Metabolism ◽  
Glucose Tolerance ◽  
Knockout Mice ◽  
Metabolic Disorders ◽  
Physiological Effects ◽  
Double Knockout ◽  
Adipose Tissues ◽  
Diet Induced Obesity ◽  
Specific Deletion

Fat remodeling has been extensively explored through protein deacetylation, but not yet acetylation, as a viable therapeutic approach in the management of obesity and related metabolic disorders. Here, we investigated the functions of key acetyltransferases CBP/p300 in adipose remodeling and their physiological effects by generating adipose-specific deletion of CBP (Cbp-AKO), p300 (p300-AKO) and double-knockout (Cbp/p300-AKO) models. We demonstrated that Cbp-AKO exhibited marked brown remodeling of inguinal WAT (iWAT) but not epididymal WAT (eWAT) after cold exposure and that this pattern was exaggerated in diet-induced obesity (DIO). Despite this striking browning phenotype, loss of Cbp was insufficient to impact body weight or glucose tolerance. In contrast, ablation of p300 in adipose tissues had minimal effects on fat remodeling and adiposity. Surprisingly, double-knockout mice (Cbp/p300-AKO) developed severe lipodystrophy along with marked hepatic steatosis, hyperglycemia and hyperlipidemia. Furthermore, we demonstrated that pharmacological inhibition of Cbp and p300 activity suppressed adipogenesis. Collectively, these data suggest that (i) CBP, but not p300, has distinct functions in regulating fat remodeling and that this occurs in a depot-selective manner; (ii) brown remodeling occurs independently of the improvements in glucose metabolism and obesity and (iii) the combined roles of CBP and p300 are indispensable for normal adipose development.

scholarly journals No Adverse Programming by Post-Weaning Dietary Fructose of Body Weight, Adiposity, Glucose Tolerance, or Metabolic Flexibility

2017 ◽  
Vol 62 (2) ◽  
pp. 1700315 ◽  
Author(s):  
Lianne M. S. Bouwman ◽  
José M. S. Fernández-Calleja ◽  
Hans J. M. Swarts ◽  
Inge van der Stelt ◽  
Annemarie Oosting ◽  
...  
Keyword(s):  
Body Weight ◽  
Glucose Tolerance ◽  
Metabolic Flexibility ◽  
Dietary Fructose

scholarly journals Insulin sensitivity and metabolic flexibility following exercise training among different obese insulin-resistant phenotypes

2013 ◽  
Vol 305 (10) ◽  
pp. E1292-E1298 ◽  
Author(s):  
Steven K. Malin ◽  
Jacob M. Haus ◽  
Thomas P. J. Solomon ◽  
Alecia Blaszczak ◽  
Sangeeta R. Kashyap ◽  
...  
Keyword(s):  
Insulin Sensitivity ◽  
Exercise Training ◽  
Glucose Tolerance ◽  
Glucose Disposal ◽  
Oral Glucose ◽  
Metabolic Flexibility ◽  
Euglycemic Hyperinsulinemic Clamp ◽  
Hepatic Insulin Sensitivity ◽  
Peripheral Insulin Sensitivity ◽  
Chronic Hyperglycemia

Impaired fasting glucose (IFG) blunts the reversal of impaired glucose tolerance (IGT) after exercise training. Metabolic inflexibility has been implicated in the etiology of insulin resistance; however, the efficacy of exercise on peripheral and hepatic insulin sensitivity or substrate utilization in adults with IFG, IGT, or IFG + IGT is unknown. Twenty-four older (66.7 ± 0.8 yr) obese (34.2 ± 0.9 kg/m2) adults were categorized as IFG ( n = 8), IGT ( n = 8), or IFG + IGT ( n = 8) according to a 75-g oral glucose tolerance test (OGTT). Subjects underwent 12-wk of exercise (60 min/day for 5 days/wk at ∼85% HRmax) and were instructed to maintain a eucaloric diet. A euglycemic hyperinsulinemic clamp (40 mU·m2·min−1) with [6,6-2H]glucose was used to determine peripheral and hepatic insulin sensitivity. Nonoxidative glucose disposal and metabolic flexibility [insulin-stimulated respiratory quotient (RQ) minus fasting RQ] were also assessed. Glucose incremental area under the curve (iAUCOGTT) was calculated from the OGTT. Exercise increased clamp-derived peripheral and hepatic insulin sensitivity more in adults with IFG or IGT alone than with IFG + IGT ( P < 0.05). Exercise reduced glucose iAUCOGTT in IGT only ( P < 0.05), and the decrease in glucose iAUCOGTT was inversely correlated with the increase in peripheral but not hepatic insulin sensitivity ( P < 0.01). Increased clamp-derived peripheral insulin sensitivity was also correlated with enhanced metabolic flexibility, reduced fasting RQ, and higher nonoxidative glucose disposal ( P < 0.05). Adults with IFG + IGT had smaller gains in clamp-derived peripheral insulin sensitivity and metabolic flexibility, which was related to blunted improvements in postprandial glucose. Additional work is required to assess the molecular mechanism(s) by which chronic hyperglycemia modifies insulin sensitivity following exercise training.

Two Weeks of Interval Training Improves Metabolic Flexibility and Glucose Tolerance in People with Prediabetes

2017 ◽  
Vol 49 (5S) ◽  
pp. 160
Author(s):  
Nicole M. Gilbertson ◽  
Natalie ZM Eichner ◽  
Jacquelyn R. Moxey ◽  
Julian M. Gaítan ◽  
Zhenqi Liu ◽  
...  
Keyword(s):  
Glucose Tolerance ◽  
Interval Training ◽  
Metabolic Flexibility

1251-P: Pancreatic ß-Cell Specific Deletion of Complement 1q Like-3 Secreted Protein Improves Glucose Tolerance by Increasing Insulin Secretion

Diabetes ◽  
2021 ◽  
Vol 70 (Supplement 1) ◽  
pp. 1251-P
Author(s):  
MOSTAFIZUR RAHMAN ◽  
HAIFA ALSHARIF ◽  
JOHN E. TROMBLEY ◽  
ASMITA PATHAK ◽  
SUSHANT BHATNAGAR
Keyword(s):  
Insulin Secretion ◽  
Glucose Tolerance ◽  
Secreted Protein ◽  
Specific Deletion

scholarly journals Abnormal Glucose Tolerance Is Associated with a Reduced Myocardial Metabolic Flexibility in Patients with Dilated Cardiomyopathy

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Domenico Tricò ◽  
Simona Baldi ◽  
Silvia Frascerra ◽  
Elena Venturi ◽  
Paolo Marraccini ◽  
...  
Keyword(s):  
Glucose Tolerance ◽  
Dilated Cardiomyopathy ◽  
Glucose Uptake ◽  
Normal Glucose Tolerance ◽  
Metabolic Flexibility ◽  
Myocardial Uptake ◽  
Abnormal Glucose Tolerance ◽  
Nonesterified Fatty Acids ◽  
Myocardial Glucose Uptake ◽  
Oxidation Rates

Dilated cardiomyopathy (DCM) is characterized by a metabolic shift from fat to carbohydrates and failure to increase myocardial glucose uptake in response to workload increments. We verified whether this pattern is influenced by an abnormal glucose tolerance (AGT). In 10 patients with DCM, 5 with normal glucose tolerance (DCM-NGT) and 5 with AGT (DCM-AGT), and 5 non-DCM subjects with AGT (N-AGT), we measured coronary blood flow and arteriovenous differences of oxygen and metabolites duringRest,Pacing(at 130 b/min), andRecovery. Myocardial lactate exchange and oleate oxidation were also measured. AtRest, DCM patients showed a reduced nonesterified fatty acids (NEFA) myocardial uptake, while glucose utilization increased only in DCM-AGT. In response toPacing, glucose uptake promptly rose in N-AGT (from 72 ± 21 to 234 ± 73 nmol/min/g,p<0.05), did not change in DCM-AGT, and slowly increased in DCM-NGT. DCM-AGT sustained the extra workload by increasing NEFA oxidation (from 1.3 ± 0.2 to 2.9 ± 0.1 μmol/min/gO2equivalents,p<0.05), while DCM-NGT showed a delayed increase in glucose uptake. Substrate oxidation rates paralleled the metabolites data. The presence of AGT in patients with DCM exacerbates both the shift from fat to carbohydrates in resting myocardial metabolism and the reduced myocardial metabolic flexibility in response to an increased workload. This trial is registered with ClinicalTrial.govNCT02440217.

scholarly journals Similar Metabolic Health in Overweight/Obese Individuals With Contrasting Metabolic Flexibility to an Oral Glucose Tolerance Test

2021 ◽  
Vol 8 ◽  
Author(s):  
Rodrigo Fernández-Verdejo ◽  
Lorena Malo-Vintimilla ◽  
Juan Gutiérrez-Pino ◽  
Antonio López-Fuenzalida ◽  
Pablo Olmos ◽  
...  
Keyword(s):  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Oral Glucose Tolerance Test ◽  
Glucose Tolerance Test ◽  
Subcutaneous Fat ◽  
Tolerance Test ◽  
Metabolic Health ◽  
Oral Glucose ◽  
Metabolic Flexibility ◽  
Oral Glucose Tolerance

Background: Low metabolic flexibility (MetF) may be an underlying factor for metabolic health impairment. Individuals with low MetF are thus expected to have worse metabolic health than subjects with high MetF. Therefore, we aimed to compare metabolic health in individuals with contrasting MetF to an oral glucose tolerance test (OGTT).Methods: In individuals with excess body weight, we measured MetF as the change in respiratory quotient (RQ) from fasting to 1 h after ingestion of a 75-g glucose load (i.e., OGTT). Individuals were then grouped into low and high MetF (Low-MetF n = 12; High-MetF n = 13). The groups had similar body mass index, body fat, sex, age, and maximum oxygen uptake. Metabolic health markers (clinical markers, insulin sensitivity/resistance, abdominal fat, and intrahepatic fat) were compared between groups.Results: Fasting glucose, triglycerides (TG), and high-density lipoprotein (HDL) were similar between groups. So were insulin sensitivity/resistance, visceral, and intrahepatic fat. Nevertheless, High-MetF individuals had higher diastolic blood pressure, a larger drop in TG concentration during the OGTT, and a borderline significant (P = 0.05) higher Subcutaneous Adipose Tissue (SAT). Further, compared to Low-MetF, High-MetF individuals had an about 2-fold steeper slope for the relationship between SAT and fat mass index.Conclusion: Individuals with contrasting MetF to an OGTT had similar metabolic health. Yet High-MetF appears related to enhanced circulating TG clearance and enlarged subcutaneous fat.

Abstract 58: Adipose-Specific Deletion of ARV1 Results in Decreased HDL Cholesterol, Reduced White Adipose Tissue Mass and Improved Glucose Tolerance in Mice

2012 ◽  
Vol 32 (suppl_1) ◽  
Author(s):  
William R Lagor ◽  
Fumin Tong ◽  
David W Fields ◽  
Wen Lin ◽  
Jeffrey T Billheimer ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Glucose Tolerance ◽  
Lipoprotein Metabolism ◽  
Hdl Cholesterol ◽  
Sphingolipid Metabolism ◽  
Chow Diet ◽  
Tissue Mass ◽  
Adipose Tissue Mass ◽  
Important Player ◽  
Specific Deletion

ACAT related enzyme 2 required for viability 1 (ARV1) was identified as a gene required for viability in yeast in the absence of cholesterol esterification. ARV1 encodes a putative lipid transporter believed to be important in trafficking of lipids from the ER to the Golgi. ARV1 deficient yeast exhibit profound alterations in cholesterol, phospholipid, and sphingolipid metabolism, accompanied by a constitutively activated unfolded protein response and impaired GPI anchor synthesis. To study the role of ARV1 in mammalian lipid metabolism, we have generated mice with an adipose specific deletion of ARV1 using Cre/loxP technology with Cre expression driven by the Ap2 promoter. ARV1 adipose specific knockout (ASKO) mice exhibited significant reductions in plasma total cholesterol (↓21%, p < 0.05), HDL cholesterol (↓25%, p < 0.01), and phospholipid (↓17.6%, p < 0.05) levels, while fasting triglyceride levels were unaffected. ARV1 ASKO mice also had substantial reductions in epididymal adipose (WT: 0.41 +/- 0.07 g vs. KO: 0.10 +/- 0.07 g, p = 0.0002) and subcutaneous adipose tissue mass (WT: 0.32 +/- 0.03 g vs. KO: 0.11 +/- 0.08 g; p= 0.0002) on a chow diet. In contrast to nearly every other lipodystrophic mouse model, the reduced fat mass in these animals was paradoxically accompanied by improved glucose tolerance (WT AUC: 32,055 vs. KO AUC: 21,470 mg/dl*minutes, p<0.05). These data identify mammalian ARV1 as an important player in adipose tissue biology, and support an important role for adipose tissue in circulating lipoprotein metabolism.

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