Very-Low-Calorie Diet Increases Myocardial Triglyceride Content and Decreases Diastolic Left Ventricular Function in Type 2 Diabetes With Cardiac Complications

Jonker, Jacqueline T.; Djaberi, Roxana; Schinkel, Linda D. van; Hammer, Sebastiaan; Bus, Mieke T. J.; Kerpershoek, Gijs; Kharagjitsingh, Aan V.; Romijn, Johannes A.; Bax, Jeroen J.; Jukema, J. Wouter; Roos, Albert de; Smit, Johannes W. A.; Lamb, Hildo J.

doi:10.2337/dc13-1423

Cited by 14 publications

(11 citation statements)

References 4 publications

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“…In this study we examined the ability of CR to alleviate diabetic cardiomyopathy and to identify the key pathways involved in CR mediated cardioprotection. CR is consider to be metabolic protective, however there are conflicting report as to its effects on the heart in diabetes [ 42 ]. There are numerous pathways involved in different models of cardiomyopathy [ 43 ].…”

Section: Resultsmentioning

confidence: 99%

Regulation of diabetic cardiomyopathy by caloric restriction is mediated by intracellular signaling pathways involving ‘SIRT1 and PGC-1α’

Waldman

Cohen

Yadin

et al. 2018

Cardiovasc Diabetol

137

131

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BackgroundMetabolic disorders such as obesity, insulin resistance and type 2 diabetes mellitus (DM2) are all linked to diabetic cardiomyopathy that lead to heart failure. Cardiomyopathy is initially characterized by cardiomyocyte hypertrophy, followed by mitochondrial dysfunction and fibrosis, both of which are aggravated by angiotensin. Caloric restriction (CR) is cardioprotective in animal models of heart disease through its catabolic activity and activation of the expression of adaptive genes. We hypothesized that in the diabetic heart; this effect involves antioxidant defenses and is mediated by SIRT1 and the transcriptional coactivator PGC-1α (Peroxisome proliferator-activated receptor-γ coactivator).MethodsObese Leptin resistant (db/db) mice characterized by DM2 were treated with angiotensin II (AT) for 4 weeks to enhance the development of cardiomyopathy. Mice were concomitantly either on a CR diet or fed ad libitum. Cardiomyocytes were exposed to high levels of glucose and were treated with EX-527 (SIRT1 inhibitor). Cardiac structure and function, gene and protein expression and oxidative stress parameters were analyzed.ResultsAT treated db/db mice developed cardiomyopathy manifested by elevated levels of serum glucose, cholesterol and cardiac hypertrophy. Leukocyte infiltration, fibrosis and an increase in an inflammatory marker (TNFα) and natriuretic peptides (ANP, BNP) gene expression were also observed. Oxidative stress was manifested by low SOD and PGC-1α levels and an increase in ROS and MDA. DM2 resulted in ERK1/2 activation. CR attenuated all these deleterious perturbations and prevented the development of cardiomyopathy. ERK1/2 phosphorylation was reduced in CR mice (p = 0.008). Concomitantly CR prevented the reduction in SIRT activity and PGC-1α (p < 0.04). Inhibition of SIRT1 activity in cardiomyocytes led to a marked reduction in both SIRT1 and PGC-1α. ROS levels were significantly (p < 0.03) increased by glucose and SIRT1 inhibition.ConclusionIn the current study we present evidence of the cardioprotective effects of CR operating through SIRT1 and PGC-1 α, thereby decreasing oxidative stress, fibrosis and inflammation. Our results suggest that increasing SIRT1 and PGC-1α levels offer new therapeutic approaches for the protection of the diabetic heart.

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Section: Resultsmentioning

confidence: 99%

Regulation of diabetic cardiomyopathy by caloric restriction is mediated by intracellular signaling pathways involving ‘SIRT1 and PGC-1α’

Waldman

Cohen

Yadin

et al. 2018

Cardiovasc Diabetol

137

131

View full text Add to dashboard Cite

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“…Dietary restriction with weight loss has been shown to improve cardiac function, increase the cardiac phosphocreatine-to-ATP ratio, and reduce myocardial NEFA uptake, cardiac workload, and intramyocardial TG (9,13,34,46). On the other hand, a very recent study in subjects with type 2 diabetes and coronary artery disease demonstrated an increase in intramyocardial TG and reduced left ventricular function after 3 days of a very low calorie diet (12). A recent systematic review suggests that diastolic ventricular function assessed by echocardiography improves with bariatric surgery and weight loss (45), although a recent study on a small number of subjects with type 2 diabetes did not demonstrate improvement in ventricular function and intramyocardial TG using magnetic resonance imaging in that setting (44).…”

Section: Discussionmentioning

confidence: 99%

Improved cardiac function and dietary fatty acid metabolism after modest weight loss in subjects with impaired glucose tolerance

Labbé

Noll

Grenier-Larouche

et al. 2014

American Journal of Physiology-Endocrinology and Metabolism

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“…Whilst the combination of improved insulin sensitivity and weight loss should be beneficial to the cardiovascular system [6], this may well not be the case due to the elevation in circulating free fatty acid (FFA) levels that occurs during rapid mobilisation of fat stores. Acute elevation of FFA levels has been shown to impair vascular function in humans [7], and lead to myocardial lipid accumulation and dysfunction in animals [8, 9], with a 3-day extreme VLCD (471 kcal/day) in humans also resulting in impaired diastolic function [10, 11].…”

Section: Introductionmentioning

confidence: 99%

Very low calorie diets are associated with transient ventricular impairment before reversal of diastolic dysfunction in obesity

et al. 2018

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ObjectivesVery low calorie diets (VLCDs) are effective at clearing hepatic steatosis and improving insulin sensitivity. Whilst long-term weight loss is beneficial to the cardiovascular system, the acute elevation in fatty acids during caloric restriction is potentially detrimental to cardiac metabolism and function. We sought to investigate any cardiovascular changes occurring over the course of a modern VLCD regime, alongside the expected peripheral metabolic improvements.Methods25 obese volunteers (BMI 36.8 ± 5.8 kg/m2) underwent magnetic resonance imaging, echocardiography, metabolic profiling, and bio-impedance analysis before 1 and 8 weeks following a VLCD (800 kcal/day). Results were compared to 15 age- and sex-matched controls.ResultsAfter 1 week of VLCD, despite only modest weight loss, significant drops occurred in liver fat and insulin resistance (HOMA-IR; by 14–50%, all p < 0.01). In contrast, myocardial triglyceride content (MTGC) increased (by 48%, p = 0.030), and was associated with deterioration in both systolic (LVEF by 4%, p = 0.041) and diastolic function (e/e′ 8.6 ± 1.4 to 9.4 ± 1.7, p = 0.019). Aortic stiffness also increased by 35% (p = 0.015).At 8 weeks, liver steatosis and visceral fat were lower than baseline (by 20–55%, p < 0.001), and peripheral metabolic improvements continued. MTGC also fell to below baseline (1.5 ± 0.6 vs 2.1 ± 1%, p = 0.05) with improved myocardial function (e/e′ 8.6 ± 1.4 to 7.5 ± 1.5, p = 0.003).ConclusionsWhilst VLCDs result in dramatic improvements in insulin resistance, they are associated with transient but significant cardiovascular functional decline, which may have an impact on those with the coexisting cardiac disease. However, after 8 weeks, the diet was associated with normalisation of cardiac function, suggesting they may form a potential therapeutic intervention for diastolic dysfunction in obesity and diabetes.

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Very-Low-Calorie Diet Increases Myocardial Triglyceride Content and Decreases Diastolic Left Ventricular Function in Type 2 Diabetes With Cardiac Complications

Cited by 14 publications

References 4 publications

Regulation of diabetic cardiomyopathy by caloric restriction is mediated by intracellular signaling pathways involving ‘SIRT1 and PGC-1α’

Regulation of diabetic cardiomyopathy by caloric restriction is mediated by intracellular signaling pathways involving ‘SIRT1 and PGC-1α’

Improved cardiac function and dietary fatty acid metabolism after modest weight loss in subjects with impaired glucose tolerance

Very low calorie diets are associated with transient ventricular impairment before reversal of diastolic dysfunction in obesity

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