scholarly journals Dietary Fat and Sugar Differentially Affect β-Adrenergic Stimulation of Cardiac ERK and AKT Pathways in C57BL/6 Male Mice Subjected to High-Calorie Feeding

2020 ◽  
Vol 150 (5) ◽  
pp. 1041-1050
Author(s):  
Sadia Ashraf ◽  
Gizem Yilmaz ◽  
Xu Chen ◽  
Romain Harmancey
Keyword(s):  
Signaling Pathways ◽  
Dietary Fat ◽  
Tolerance Test ◽  
Whole Body ◽  
Adrenergic Stimulation ◽  
High Fat ◽  
Cardiac Growth ◽  
Regulatory Pathways ◽  
High Sugar ◽  
Stimulation Of

ABSTRACT Background High dietary fat and sugar promote cardiac hypertrophy independently from an increase in blood pressure. The respective contribution that each macronutrient exerts on cardiac growth signaling pathways remains unclear. Objective The goal of this study was to investigate the mechanisms by which high amounts of dietary fat and sugar affect cardiac growth regulatory pathways. Methods Male C57BL/6 mice (9 wk old; n = 20/group) were fed a standard rodent diet (STD; kcal% protein-fat-carbohydrate, 29-17-54), a high-fat diet (HFD; 20-60-20), a high-fat and high-sugar Western diet (WD; 20-45-35), a high-sugar diet with mixed carbohydrates (HCD; 20-10-70), or a high-sucrose diet (HSD; 20-10-70). Body composition was assessed weekly by EchoMRI. Whole-body glucose utilization was assessed with an intraperitoneal glucose tolerance test. After 6 wk on diets, mice were treated with saline or 20 mg/kg isoproterenol (ISO), and the activity of cardiac growth regulatory pathways was analyzed by immunoblotting. Data were analyzed by ANOVA with data from the STD group included for references only. Results Compared with HCD and HSD, WD and HFD increased body fat mass 2.7- to 3.8-fold (P < 0.001), induced glucose intolerance (P < 0.001), and increased insulin concentrations >1.5-fold (P < 0.05), thereby enhancing basal and ISO-stimulated AKT phosphorylation at both threonine 308 and serine 473 residues (+25−63%; P < 0.05). Compared with HFD, the high-sugar diets potentiated ISO-mediated stimulation of the glucose-sensitive kinases PYK2 (>47%; P < 0.05 for HCD and HSD) and ERK (>34%; P < 0.05 for WD, HCD, and HSD), thereby leading to increased phosphorylation of protein synthesis regulator S6K1 at threonine 389 residue (>64%; P < 0.05 for WD, HCD, and HSD). Conclusions Dietary fat and sugar affect cardiac growth signaling pathways in C57BL/6 mice through distinct and additive mechanisms. The findings may provide new insights into the role of overnutrition in pathological cardiac remodeling.

scholarly journals APP deficiency results in resistance to obesity but impairs glucose tolerance upon high fat feeding

2018 ◽  
Vol 237 (3) ◽  
pp. 311-322 ◽  
Author(s):  
Juliane K Czeczor ◽  
Amanda J Genders ◽  
Kathryn Aston-Mourney ◽  
Timothy Connor ◽  
Liam G Hall ◽  
...  
Keyword(s):  
Energy Expenditure ◽  
Glucose Tolerance ◽  
Cell Mass ◽  
Tolerance Test ◽  
Whole Body ◽  
Dark Phase ◽  
High Fat ◽  
Neuronal Metabolism ◽  
Fat Feeding ◽  
Deficient Mice

The amyloid precursor protein (APP) generates a number of peptides when processed through different cleavage mechanisms, including the amyloid beta peptide that is implicated in the development of Alzheimer’s disease. It is well established that APP via its cleaved peptides regulates aspects of neuronal metabolism. Emerging evidence suggests that amyloidogenic processing of APP can lead to altered systemic metabolism, similar to that observed in metabolic disease states. In the present study, we investigated the effect of APP deficiency on obesity-induced alterations in systemic metabolism. Compared with WT littermates, APP-deficient mice were resistant to diet-induced obesity, which was linked to higher energy expenditure and lipid oxidation throughout the dark phase and was associated with increased spontaneous physical activity. Consistent with this lean phenotype, APP-deficient mice fed a high-fat diet (HFD) had normal insulin tolerance. However, despite normal insulin action, these mice were glucose intolerant, similar to WT mice fed a HFD. This was associated with reduced plasma insulin in the early phase of the glucose tolerance test. Analysis of the pancreas showed that APP was required to maintain normal islet and β-cell mass under high fat feeding conditions. These studies show that, in addition to regulating aspects of neuronal metabolism, APP is an important regulator of whole body energy expenditure and glucose homeostasis under high fat feeding conditions.

Energy expenditure in humans: effects of dietary fat and carbohydrate

1990 ◽  
Vol 258 (2) ◽  
pp. E347-E351 ◽  
Author(s):  
W. G. Abbott ◽  
B. V. Howard ◽  
G. Ruotolo ◽  
E. Ravussin
Keyword(s):  
Energy Expenditure ◽  
Dietary Fat ◽  
Weight Maintenance ◽  
Caloric Intake ◽  
Insulin Dependent Diabetes Mellitus ◽  
Whole Body ◽  
Dependent Diabetes Mellitus ◽  
Pima Indians ◽  
High Fat ◽  
High Carbohydrate

A high-dietary fat intake may be an important environmental factor leading to obesity in some people. The mechanism could be either a decrease in energy expenditure and/or an increase in caloric intake. To determine the relative importance of these mechanisms we measured 24-h energy expenditure in a whole body calorimeter in 14 nondiabetic subjects and in six subjects with non-insulin-dependent diabetes mellitus, eating isocaloric, weight-maintenance, high-fat, and high-carbohydrate diets. All subjects were Pima Indians. In nondiabetics, the mean total 24-h energy expenditure was similar (2,436 +/- 103 vs. 2,359 +/- 82 kcal/day) on high-fat and high-carbohydrate diets, respectively. The means for sleeping and resting metabolic rates, thermic effect of food, and spontaneous physical activity were unchanged. Similar results were obtained in the diabetic subjects. In summary, using a whole body calorimeter, we found no evidence of a decrease in 24-h energy expenditure on a high-fat diet compared with a high-carbohydrate diet.

scholarly journals PL-017 High-fat overfeeding increases intramuscular triglyceride content and perilipin protein expression in human skeletal muscle

2018 ◽  
Vol 1 (1) ◽  
Author(s):  
Katie Whytock ◽  
Siôn Parry ◽  
Mark Turner ◽  
Lewis James ◽  
Richard Fergusson ◽  
...  
Keyword(s):  
Dietary Intervention ◽  
Insulin Signalling ◽  
Tolerance Test ◽  
Whole Body ◽  
Future Research ◽  
Oral Glucose ◽  
Type I ◽  
High Fat ◽  
Intramuscular Triglyceride ◽  
High Calorie

Objective High-fat high-calorie diets can induce whole body insulin resistance (IR) whilst increasing stores of intramuscular triglyceride (IMTG) contained within lipid droplets (LD). Perilipin (PLIN) proteins assist in IMTG storage. Synaptosomal-associated protein (SNAP23) may support LD growth and also direct IMTG-derived fatty acids (FA) to mitochondria for β-oxidation. The objectives of this study were: 1) to test the hypothesis that 7 days of high-fat overfeeding increases IMTG content to prevent lipid induced muscle IR and 2) identify changes in PLINs, SNAP23 and mitochondria content and colocalisation of PLINs with LD, and SNAP23 with LD and mitochondria. Methods Muscle biopsies were obtained from thevastus lateralisof thirteen healthy individuals (age: 23±1years, BMI: 24.4±0.7kg.m-2) before (0min) and during (30min) an oral glucose tolerance test (OGTT), pre and post 7-days consuming a high-fat (65% energy) high-calorie (+50% kcal) diet. IMTG, PLIN2, PLIN3, PLIN5, SNAP23 and mitochondria content were measured using (semi)-quantitative confocal immunofluorescence microscopy. PLIN2, PLIN3 and PLIN5 colocalisation to LD was measured using object-based colocalisation analyses. Pearson’s correlation coefficient quantified colocalisation between SNAP23 and plasma membrane (PM), mitochondria and LD. Phosphorylation of intermediates of the muscle insulin-signalling cascade (Akt and AS160) were measured at 0 and 30 min of the OGTT before and after the dietary intervention. Results Following overfeeding phosphorylation of Akt and AS160 in muscle was not impaired during the OGTT, however Matsuda index of whole-body insulin sensitivity decreased (-23%; P < 0.01). IMTG content increased in type I fibres (+100%; P < 0.001) due to both an increase in LD number (+43%; P < 0.001) and size (+44%; P< 0.001). Of the PLINs investigated, only PLIN3 content increased (+50%;P < 0.01) exclusively in type I fibres. PLIN2-associated LD increased (+80%; P < 0.01) in type I fibres only, whereas PLIN3 and PLIN5-associated LD were unaltered. SNAP23 and mitochondria content did not change, nor did the colocalisation of SNAP23 with the PM, mitochondria or LD. Conclusions Our data confirm the hypothesis that following high-fat overfeeding IMTG stores increased whilst activation of key muscle insulin signalling components were maintained. The increase in IMTG stores is likely supported by the concurrent increase in total PLIN3 content and a redistribution of existing stores of PLIN2 to the expanded LD pool in type I fibres. To confirm if increased IMTG storage protects muscle from IR future research should determine whether meal-derived FAs are directed to IMTG rather than ceramides and diacylglycerol.

scholarly journals High-Fat Overfeeding Impairs Peripheral Glucose Metabolism and Muscle Microvascular eNOS Ser1177 Phosphorylation

2019 ◽  
Vol 105 (1) ◽  
pp. 65-77 ◽  
Author(s):  
Siôn A Parry ◽  
Mark C Turner ◽  
Rachel M Woods ◽  
Lewis J James ◽  
Richard A Ferguson ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Glycemic Control ◽  
Insulin Signaling ◽  
Dietary Fat ◽  
Glucose Production ◽  
Endogenous Glucose Production ◽  
Whole Body ◽  
High Fat ◽  
Before And After ◽  
Protein Ingestion

Abstract Context The mechanisms responsible for dietary fat-induced insulin resistance of skeletal muscle and its microvasculature are only partially understood. Objective To determine the impact of high-fat overfeeding on postprandial glucose fluxes, muscle insulin signaling, and muscle microvascular endothelial nitric oxide synthase (eNOS) content and activation. Design Fifteen non-obese volunteers consumed a high-fat (64%) high-energy (+47%) diet for 7 days. Experiments were performed before and after the diet. Stable isotope tracers were used to determine glucose fluxes in response to carbohydrate plus protein ingestion. Muscle insulin signaling was determined as well as the content and activation state of muscle microvascular eNOS. Results High-fat overfeeding impaired postprandial glycemic control as demonstrated by higher concentrations of glucose (+11%; P = 0.004) and insulin (+19%; P = 0.035). Carbohydrate plus protein ingestion suppressed endogenous glucose production to a similar extent before and after the diet. Conversely, high-fat overfeeding reduced whole-body glucose clearance (–16%; P = 0.021) and peripheral insulin sensitivity (–26%; P = 0.006). This occurred despite only minor alterations in skeletal muscle insulin signaling. High-fat overfeeding reduced eNOS content in terminal arterioles (P = 0.017) and abolished the increase in eNOS Ser1177 phosphorylation that was seen after carbohydrate plus protein ingestion. Conclusion High-fat overfeeding impaired whole-body glycemic control due to reduced glucose clearance, not elevated endogenous glucose production. The finding that high-fat overfeeding abolished insulin-mediated eNOS Ser1177 phosphorylation in the terminal arterioles suggests that impairments in the vasodilatory capacity of the skeletal muscle microvasculature may contribute to early dietary fat-induced impairments in glycemic control.

scholarly journals Long-term niacin treatment induces insulin resistance and adrenergic responsiveness in adipocytes by adaptive downregulation of phosphodiesterase 3B

2014 ◽  
Vol 306 (7) ◽  
pp. E808-E813 ◽  
Author(s):  
Mattijs M. Heemskerk ◽  
Sjoerd A. A. van den Berg ◽  
Amanda C. M. Pronk ◽  
Jan-Bert van Klinken ◽  
Mariëtte R. Boon ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Tolerance Test ◽  
Lipid Lowering ◽  
Whole Body ◽  
Adrenergic Stimulation ◽  
Nonesterified Fatty Acids ◽  
Insulin Resistant ◽  
Phosphodiesterase 3B ◽  
Camp Stimulation

The lipid-lowering effect of niacin has been attributed to the inhibition of cAMP production in adipocytes, thereby inhibiting intracellular lipolysis and release of nonesterified fatty acids (NEFA) to the circulation. However, long-term niacin treatment leads to a normalization of plasma NEFA levels and induces insulin resistance, for which the underlying mechanisms are poorly understood. The current study addressed the effects of long-term niacin treatment on insulin-mediated inhibition of adipocyte lipolysis and focused on the regulation of cAMP levels. APOE*3-Leiden.CETP transgenic mice treated with niacin for 15 wk were subjected to an insulin tolerance test and showed whole body insulin resistance. Similarly, adipocytes isolated from niacin-treated mice were insulin resistant and, interestingly, exhibited an increased response to cAMP stimulation by 8Br-cAMP, β1- and β2-adrenergic stimulation. Gene expression analysis of the insulin and β-adrenergic pathways in adipose tissue indicated that all genes were downregulated, including the gene encoding the cAMP-degrading enzyme phosphodiesterase 3B (PDE3B). In line with this, we showed that insulin induced a lower PDE3B response in adipocytes isolated from niacin-treated mice. Inhibiting PDE3B with cilostazol increased lipolytic responsiveness to cAMP stimulation in adipocytes. These data show that long-term niacin treatment leads to a downregulation of PDE3B in adipocytes, which could explain part of the observed insulin resistance and the increased responsiveness to cAMP stimulation.

Adrenergic Stimulation of Regional Plasminogen Activator Release in Rabbits

1992 ◽  
Vol 68 (05) ◽  
pp. 545-549 ◽  
Author(s):  
W L Chandler ◽  
S C Loo ◽  
D Mornin
Keyword(s):  
Lower Extremity ◽  
Plasminogen Activator ◽  
Beta Blocker ◽  
Time Course ◽  
Vascular System ◽  
Adrenergic Stimulation ◽  
Epinephrine Administration ◽  
Adrenergic Antagonist ◽  
Vascular Beds ◽  
Stimulation Of

SummaryThe purpose of this study was to determine whether different regions of the rabbit vascular system show variations in the rate of plasminogen activator (PA) secretion. To start, we evaluated the time course, dose response and adrenergic specificity of PA release. Infusion of 1 µg/kg of epinephrine stimulated a 116 ± 60% (SD) increase in PA activity that peaked 30 to 60 s after epinephrine administration. Infusion of 1 µg/kg of norepinephrine, isoproterenol and phenylephrine had no effect on PA activity. Pretreatment with phentolamine, an alpha adrenergic antagonist, blocked the release of PA by epinephrine while pretreatment with the beta blocker propranolol had no effect. This suggests that PA release in the rabbit was mediated by some form of alpha receptor.Significant arterio-venous differences in basal PA activity were found across the pulmonary and splanchnic vascular beds but not the lower extremity/pelvic bed. After stimulation with epinephrine, PA activity increased 46% across the splanchnic bed while no change was seen across the lower extremity/pelvic bed. We conclude that several vascular beds contribute to circulating PA activity in the rabbit, and that these beds secrete PA at different rates under both basal and stimulated conditions.

Activation of Hageman Factor by α-Adrenergic Stimulation

1970 ◽  
Vol 23 (03) ◽  
pp. 417-422 ◽  
Author(s):  
D. G McKay ◽  
J.-G Latour ◽  
Mary H. Parrish
Keyword(s):  
Disseminated Intravascular Coagulation ◽  
Adrenergic Receptor ◽  
Adrenergic Stimulation ◽  
Hageman Factor ◽  
Intravascular Coagulation ◽  
Receptor Sites ◽  
High Doses ◽  
Stimulation Of

SummaryThe infusion of epinephrine in high doses produces disseminated intravascular coagulation by activation of Hageman factor. The effect is blocked by phenoxybenz-amine and is therefore due to stimulation of α-adrenergic receptor sites.

Sign in / Sign up

Export Citation Format

Share Document