Cafeteria diet-induced insulin resistance is not associated with decreased insulin signaling or AMPK activity and is alleviated by physical training in rats

2010 ◽  
Vol 299 (2) ◽  
pp. E215-E224 ◽  
Author(s):  
Nina Brandt ◽  
Katrien De Bock ◽  
Erik A. Richter ◽  
Peter Hespel
Keyword(s):  
Insulin Resistance ◽  
Exercise Training ◽  
Energy Intake ◽  
Insulin Signaling ◽  
Molecular Mechanisms ◽  
Cafeteria Diet ◽  
Low Fat ◽  
Low Fat Diet ◽  
Male Wistar Rats ◽  
Syntaxin 4

Excess energy intake via a palatable low-fat diet (cafeteria diet) is known to induce obesity and glucose intolerance in rats. However, the molecular mechanisms behind this adaptation are not known, and it is also not known whether exercise training can reverse it. Male Wistar rats were assigned to 12-wk intervention groups: chow-fed controls (CON), cafeteria diet (CAF), and cafeteria diet plus swimming exercise during the last 4 wk (CAFTR). CAF feeding led to increased body weight (16%, P < 0.01) and increased plasma glucose ( P < 0.05) and insulin levels ( P < 0.01) during an IVGTT, which was counteracted by training. In the perfused hindlimb, insulin-stimulated glucose transport in red gastrocnemius muscle was completely abolished in CAF and rescued by exercise training. Apart from a tendency toward an ∼20% reduction in both basal and insulin-stimulated Akt Ser473 phosphorylation ( P = 0.051) in the CAF group, there were no differences in insulin signaling (IR Tyr1150/1151, PI 3-kinase activity, Akt Thr308, TBC1D4 Thr642, GSK3-α/β Ser21/9) or changes in AMPKα1 or -α2, GLUT4, Munc18c, or syntaxin 4 protein expression or in phosphorylation of AMPK Thr172 among the groups. In conclusion, surplus energy intake of a palatable but low-fat cafeteria diet resulted in obesity and insulin resistance that was rescued by exercise training. Interestingly, insulin resistance was not accompanied by major defects in the insulin-signaling cascade or in altered AMPK expression or phosphorylation. Thus, compared with previous studies of high-fat feeding, where insulin signaling is significantly impaired, the mechanism by which CAF diet induces insulin resistance seems different.

scholarly journals Insulin Resistance and Diabetes Mellitus in Alzheimer’s Disease

Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 1236
Author(s):  
Jesús Burillo ◽  
Patricia Marqués ◽  
Beatriz Jiménez ◽  
Carlos González-Blanco ◽  
Manuel Benito ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Alzheimer’S Disease ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Alzheimer's Disease ◽  
Type 2 Diabetes Mellitus ◽  
Insulin Signaling ◽  
Molecular Mechanisms ◽  
Progressive Disease

Type 2 diabetes mellitus is a progressive disease that is characterized by the appearance of insulin resistance. The term insulin resistance is very wide and could affect different proteins involved in insulin signaling, as well as other mechanisms. In this review, we have analyzed the main molecular mechanisms that could be involved in the connection between type 2 diabetes and neurodegeneration, in general, and more specifically with the appearance of Alzheimer’s disease. We have studied, in more detail, the different processes involved, such as inflammation, endoplasmic reticulum stress, autophagy, and mitochondrial dysfunction.

scholarly journals Visfatin Induces Inflammation and Insulin Resistance via the NF-κB and STAT3 Signaling Pathways in Hepatocytes

2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Yu Jung Heo ◽  
Sung-E Choi ◽  
Ja Young Jeon ◽  
Seung Jin Han ◽  
Dae Jung Kim ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Signaling Pathways ◽  
Western Blotting ◽  
Insulin Signaling ◽  
Proinflammatory Cytokine ◽  
Hepg2 Cells ◽  
Molecular Mechanisms ◽  
Immunocytochemical Staining ◽  
Mrna Levels ◽  
Rt Pcr

Background. It has been suggested that visfatin, which is an adipocytokine, exhibits proinflammatory properties and is associated with insulin resistance. Insulin resistance and inflammation are the principal pathogeneses of nonalcoholic fatty liver disease (NAFLD), but the relationship, if any, between visfatin and NAFLD remains unclear. Here, we evaluated the effects of visfatin on hepatic inflammation and insulin resistance in HepG2 cells and examined the molecular mechanisms involved. Methods. After treatment with visfatin, the inflammatory cytokines IL-6, TNF-α, and IL-1β were assessed by real-time polymerase chain reaction (RT-PCR) and immunocytochemical staining in HepG2 cells. To investigate the effects of visfatin on insulin resistance, we evaluated insulin-signaling pathways, such as IR, IRS-1, GSK, and AKT using immunoblotting. We assessed the intracellular signaling molecules including STAT3, NF-κB, IKK, p38, JNK, and ERK by western blotting. We treated HepG2 cells with both visfatin and either AG490 (a JAK2 inhibitor) or Bay 7082 (an NF-κB inhibitor); we examined proinflammatory cytokine mRNA levels using RT-PCR and insulin signaling using western blotting. Results. In HepG2 cells, visfatin significantly increased the levels of proinflammatory cytokines, reduced the levels of proteins (e.g., phospho-IR, phospho-IRS-1 (Tyr612), phospho-AKT, and phospho-GSK-3α/β) involved in insulin signaling, and increased IRS-1 S307 phosphorylation compared to controls. Interestingly, visfatin increased the activities of the JAK2/STAT3 and IKK/NF-κB signaling pathways but not those of the JNK, p38, and ERK pathways. Visfatin-induced inflammation and insulin resistance were regulated by JAK2/STAT3 and IKK/NF-κB signaling; together with AG490 or Bay 7082, visfatin significantly reduced mRNA levels of IL-6, TNF-α and IL-1β and rescued insulin signaling. Conclusion. Visfatin induced proinflammatory cytokine production and inhibited insulin signaling via the STAT3 and NF-κB pathways in HepG2 cells.

scholarly journals Effects of food pattern change and physical exercise on cafeteria diet-induced obesity in female rats

2012 ◽  
Vol 108 (8) ◽  
pp. 1511-1518 ◽  
Author(s):  
Jéferson F. Goularte ◽  
Maria B. C. Ferreira ◽  
Gilberto L. Sanvitto
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Insulin Sensitivity ◽  
Physical Exercise ◽  
Energy Intake ◽  
Liver Weight ◽  
Cafeteria Diet ◽  
Chow Diet ◽  
Diet Induced Obesity ◽  
Visceral Adipose

Obesity affects a large number of people around the world and appears to be the result of changes in food intake, eating habits and physical activity levels. Changes in dietary patterns and physical exercise are therefore strongly recommended to treat obesity and its complications. The present study tested the hypothesis that obesity and metabolic changes produced by a cafeteria diet can be prevented with dietary changes and/or physical exercise. A total of fifty-six female Wistar rats underwent one of five treatments: chow diet; cafeteria diet; cafeteria diet followed by a chow diet; cafeteria diet plus exercise; cafeteria diet followed by a chow diet plus exercise. The duration of the experiment was 34 weeks. The cafeteria diet resulted in higher energy intake, weight gain, increased visceral adipose tissue and liver weight, and insulin resistance. The cafeteria diet followed by the chow diet resulted in energy intake, body weight, visceral adipose tissue and liver weight and insulin sensitivity equal to that of the controls. Exercise increased total energy intake at week 34, but produced no changes in the animals' body weight or adipose tissue mass. However, insulin sensitivity in animals subjected to exercise and the diet was similar to that of the controls. The present study found that exposure to palatable food caused obesity and insulin resistance and a diet change was sufficient to prevent cafeteria diet-induced obesity and to maintain insulin sensitivity at normal levels. In addition, exercise resulted in normal insulin sensitivity in obese rats. These results may help to develop new approaches for the treatment of obesity and type 2 diabetes mellitus.

scholarly journals Herring Milt and Herring Milt Protein Hydrolysate Reduce Weight Gain and Improve Insulin Sensitivity and Pancreatic Beta-Cell Function in Diet-Induced Obese Mice

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 1699-1699
Author(s):  
Yanwen Wang ◽  
Sandhya Nair ◽  
Jacques Gagnon
Keyword(s):  
Insulin Resistance ◽  
High Fat Diet ◽  
Cell Function ◽  
Protein Hydrolysate ◽  
Oral Glucose ◽  
High Fat ◽  
Low Fat ◽  
Insulin Resistant ◽  
Low Fat Diet ◽  
Dietary Casein

Abstract Objectives The present study was designed to examine the effect of herring milt dry powder (HMDP) on glucose homeostasis and related metabolic phenotypes and compare its efficacy with herring milt protein hydrolysate (HMPH) in diet-induced obese and insulin resistant mice. Methods Male C57BL/6 J mice were pretreated with a high-fat diet for 7 weeks were divided into 3 groups where one group continued on the high-fat diet and used as the obese and insulin resistant control (HFC) and the other two groups were fed a modified HFC diet where 70% of casein was replaced with an equal percentage of protein derived from HMDP or HMPH. A group of mice fed a low-fat diet all the time was used as the normal or low-fat control (LFC). Body weight was obtained weekly and food intake was recorded daily. Semi-fating (4–6 hr) blood glucose was measured every other week using a glucometer using the blood from tail vein. Oral glucose tolerance was measured twice during weeks 5 and 9, respectively, and insulin tolerance was determined during week 7 of the treatment. At the end of the experiment, serum was obtained following overnight fasting for the measurement of fasting insulin, leptin, free fatty acids and lipids as well as other glucose metabolism-related biomarkers. Results During the 9-week treatment period, mice on the high-fat diet maintained significantly higher body weight and semi-fasting blood glucose levels and exhibited impaired oral glucose tolerance and insulin resistance relative to mice on the low-fat diet. At the end of the study, the analysis of fasting blood samples revealed that mice on the high-fat diet had increases in serum insulin, leptin, free fatty acids and cholesterol levels. Mice fed the high-fat diet also showed an increase in insulin resistance index and a decrease in β-cell function index. Compared to mice on the high-fat diet, the 70% replacement of dietary casein with an equal percentage of protein derived from HMDP or HMPH reversed or markedly improved these parameters, and HMDP and HMPH showed similar effects. Conclusions The results demonstrate that replacing dietary casein with the same amount of protein derived from either HMDP or HMPH prevents and improves high-fat-diet-induced obesity and insulin resistance. Funding Sources Atlantic Canada Opportunity Agency through the Atlantic Innovation Fund grant (no. 193,594) and National Research Council of Canada – NHP program.

scholarly journals Comprehensive functional screening of miRNAs involved in fat cell insulin sensitivity among women

2017 ◽  
Vol 312 (6) ◽  
pp. E482-E494 ◽  
Author(s):  
Ingrid Dahlman ◽  
Yasmina Belarbi ◽  
Jurga Laurencikiene ◽  
Annie M. Pettersson ◽  
Peter Arner ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Differential Expression ◽  
Insulin Signaling ◽  
Molecular Mechanisms ◽  
Functional Screening ◽  
Fat Cell ◽  
Subcutaneous White Adipose Tissue ◽  
Micro Rnas

The key pathological link between obesity and type 2 diabetes is insulin resistance, but the molecular mechanisms are not entirely identified. micro-RNAs (miRNA) are dysregulated in obesity and may contribute to insulin resistance. Our objective was to detect and functionally investigate miRNAs linked to insulin sensitivity in human subcutaneous white adipose tissue (scWAT). Subjects were selected based on the insulin-stimulated lipogenesis response of subcutaneous adipocytes. Global miRNA profiling was performed in abdominal scWAT of 18 obese insulin-resistance (OIR), 21 obese insulin-sensitive (OIS), and 9 lean women. miRNAs demonstrating differential expression between OIR and OIS women were overexpressed in human in vitro-differentiated adipocytes followed by assessment of lipogenesis and identification of miRNA targets by measuring mRNA/protein expression and 3′-untranslated region analysis. Eleven miRNAs displayed differential expression between OIR and OIS states. Overexpression of miR-143-3p and miR-652-3p increased insulin-stimulated lipogenesis in human in vitro differentiated adipocytes and directly or indirectly affected several genes/proteins involved in insulin signaling at transcriptional or posttranscriptional levels. Adipose expression of miR-143-3p and miR-652-3p was positively associated with insulin-stimulated lipogenesis in scWAT independent of body mass index. In conclusion, miR-143-3p and miR-652-3p are linked to scWAT insulin resistance independent of obesity and influence insulin-stimulated lipogenesis by interacting at different steps with insulin-signaling pathways.

TWEAK prevents TNF-α-induced insulin resistance through PP2A activation in human adipocytes

2013 ◽  
Vol 305 (1) ◽  
pp. E101-E112 ◽  
Author(s):  
Ana Vázquez-Carballo ◽  
Victòria Ceperuelo-Mallafré ◽  
Matilde R. Chacón ◽  
Elsa Maymó-Masip ◽  
Margarita Lorenzo ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Insulin Signaling ◽  
Visceral Fat ◽  
Molecular Mechanisms ◽  
Physiological Role ◽  
Metabolic Effects ◽  
Human Adipocytes ◽  
Fat Depots ◽  
Tnf Α

Visceral fat is strongly associated with insulin resistance. Obesity-associated adipose tissue inflammation and inflammatory cytokine production are considered key mediators of insulin signaling inhibition. TWEAK is a relatively new member of the TNF cytokine superfamily, which can exist as full length membrane-associated (mTWEAK) and soluble (sTWEAK) isoforms. Although TWEAK has been shown to have important functions in chronic inflammatory diseases its physiological role in adipose tissue remains unresolved. In this study, we explore the molecular mechanisms involved in the modulation of TNF-α-induced effects on insulin sensitivity by sTWEAK in a human visceral adipose cell line and also in primary human adipocytes obtained from visceral fat depots. Our data reveal that sTWEAK ameliorates TNF-α-induced insulin resistance on glucose uptake, GLUT4 translocation and insulin signaling without affecting other metabolic effects of TNF-α such as lipolysis or apoptotis. Co-immunoprecipitation experiments in adipose cells revealed that pretreatment with sTWEAK specifically inhibits TRAF2 association with TNFR1, but not with TNFR2, which mediates insulin resistance. However, sTWEAK does not affect other downstream molecules activated by TNF-α, such as TAK1. Rather, sTWEAK abolishes the stimulatory effect of TNF-α on JNK1/2, which is directly involved in the development of insulin resistance. This is associated with an increase in PP2A activity upon sTWEAK treatment. Silencing of the PP2A catalytic subunit gene overcomes the dephosphorylation effect of sTWEAK on JNK1/2, pointing to PP2A as a relevant mediator of sTWEAK-induced JNK inactivation. Overall, our data reveal a protective role of TWEAK in glucose homeostasis and identify PP2A as a new driver in the modulation of TNF-α signaling by sTWEAK.

scholarly journals Role of inhibitory κB kinase and c-Jun NH2-terminal kinase in the development of hepatic insulin resistance in critical illness diabetes

2011 ◽  
Vol 301 (3) ◽  
pp. G454-G463 ◽  
Author(s):  
Shaoning Jiang ◽  
Joseph L. Messina
Keyword(s):  
Insulin Resistance ◽  
Critical Illness ◽  
Insulin Signaling ◽  
Molecular Mechanisms ◽  
Adenovirus Vector ◽  
Dominant Negative ◽  
Serine Phosphorylation ◽  
Hepatic Insulin Resistance ◽  
Mortality And Morbidity ◽  
Hepatic Insulin Signaling

Hyperglycemia and insulin resistance induced by acute injuries or critical illness are associated with increased mortality and morbidity, as well as later development of type 2 diabetes. The molecular mechanisms underlying the acute onset of insulin resistance following critical illness remain poorly understood. In the present studies, the roles of serine kinases, inhibitory κB kinase (IKK) and c-Jun NH2-terminal kinase (JNK), in the acute development of hepatic insulin resistance were investigated. In our animal model of critical illness diabetes, activation of hepatic IKK and JNK was observed as early as 15 min, concomitant with the rapid impairment of hepatic insulin signaling and increased serine phosphorylation of insulin receptor substrate 1. Inhibition of IKKα or IKKβ, or both, by adenovirus vector-mediated expression of dominant-negative IKKα or IKKβ in liver partially restored insulin signaling. Similarly, inhibition of JNK1 kinase by expression of dominant-negative JNK1 also resulted in improved hepatic insulin signaling, indicating that IKK and JNK1 kinases contribute to critical illness-induced insulin resistance in liver.

scholarly journals Objective versus Self-Reported Energy Intake Changes During Low-Carbohydrate and Low-Fat Diets

2018 ◽  
Author(s):  
Juen Guo ◽  
Jennifer L. Robinson ◽  
Christopher Gardner ◽  
Kevin D. Hall
Keyword(s):  
Energy Intake ◽  
Calorie Restriction ◽  
List Type ◽  
Low Fat ◽  
Dietary Recall ◽  
Low Carbohydrate Diet ◽  
Model Based ◽  
Low Fat Diet ◽  
Low Carbohydrate ◽  
Fat Diets

AbstractObjectiveTo examine objective versus self-reported energy intake changes (ΔEI) during a 12-month diet intervention.MethodsWe calculated ΔEI in subjects who participated in a 1-year randomized low-carbohydrate versus low-fat diet trial using repeated body weight measurements as inputs to an objective mathematical model (ΔEIModel) and compared these values with self-reported energy intake changes assessed by repeated 24-hr recalls (ΔEI24hrRecall).ResultsΔEI24hrRecall indicated a relatively persistent state of calorie restriction ≥500 kcal/d throughout the year with no significant differences between diets. ΔEIModel demonstrated large early decreases in calorie intake >800 kcal/d followed by an exponential return to approximately 100 kcal/d below baseline at the end of the year. The low-carbohydrate diet resulted in ΔEIModel that was 162±53 kcal/d lower than the low-fat diet over the first 3 months (p=0.002), but no significant diet differences were found at later times. Weight loss at 12 months was significantly related to ΔEIModel at all time intervals for both diets (p<0.0001).ConclusionsSelf-reported measurements of ΔEI were inaccurate. Model-based calculations of ΔEI found that instructions to follow the low-carbohydrate diet resulted in greater calorie restriction than the low-fat diet in the early phases of the intervention, but these diet differences were not sustained.What is already known about this subject?Diet assessments that rely on self-report, such as 24hr dietary recall, are known to underestimate actual energy intake as measured by doubly labeled water. However, it is possible that repeated self-reported measurements could accurately detect changes in energy intake over time if the absolute bias of self-reported of measurements is approximately constant for each subject.What this study addsWe compared energy intake changes measured using repeated 24hr dietary recall measurements collected over the course of the 1-year Diet Intervention Examining The Factors Interacting with Treatment Success (DIETFITS) trial versus energy intake changes calculated using repeated body weight measurements as inputs to a validated mathematical model.Whereas self-reported measurements indicated a relatively persistent state of calorie restriction, objective model-based measurements demonstrated a large early calorie restriction followed by an exponential rise in energy intake towards the pre-intervention baseline.Model-based calculations, but not self-reported measurements, found that low-carbohydrate diets led to significantly greater early decreases in energy intake compared to low-fat diets, but long-term energy intake changes were not significantly different.

Alterations in the early steps of the insulin-signaling system in skeletal muscle of GH-transgenic mice

1999 ◽  
Vol 277 (3) ◽  
pp. E447-E454 ◽  
Author(s):  
Fernando P. Dominici ◽  
Debora Cifone ◽  
Andrzej Bartke ◽  
Daniel Turyn
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Transgenic Mice ◽  
Tyrosine Phosphorylation ◽  
Insulin Signaling ◽  
Molecular Mechanisms ◽  
Kinase Activity ◽  
Signaling System ◽  
Phosphorylation State ◽  
Gh Excess

Growth hormone (GH) excess is associated with insulin resistance, but the molecular mechanisms of this association are poorly understood. In the current work, we have examined the consequences of exposure to high GH levels on the early steps of the insulin-signaling system in the muscle of bovine (b) GH-transgenic mice. The protein content and the tyrosine phosphorylation state of the insulin receptor (IR), the IR substrate-1 (IRS-1), the association between IRS-1 and the p85 subunit of phosphatidylinositol (PI) 3-kinase, and the phosphotyrosine-derived PI 3-kinase activity in this tissue were studied. We found that in skeletal muscle of bGH-transgenic mice, exposure to high circulating GH levels results in 1) reduced IR abundance, 2) reduced IR tyrosine phosphorylation, 3) reduced efficiency of IRS-1 tyrosine phosphorylation, and 4) defective activation of PI 3-kinase by insulin. These alterations may be related to the insulin resistance exhibited by these animals.

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