Weight loss enhances cardiac energy metabolism and function in heart failure associated with obesity

Karwi, Qutuba G.; Zhang, Liyan; Altamimi, Tariq; Wagg, Cory S.; Patel, Vaibhav; Uddin, Golam Mezbah; Joerg, Alice R.; Padwal, Raj; Johnstone, David E.; Sharma, Arya M.; Oudit, Gavin Y.

doi:10.1111/dom.13762

Cited by 36 publications

(45 citation statements)

References 50 publications

(90 reference statements)

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“…This research is in line with other studies and calls attention to the importance of a low body weight to decrease cardiac risk (Riordan et al, 2008;Derumeaux et al, 2017) with ventricular hypertrophy (Karwi et al, 2019). However, the influence of body weight on AMPK activation in RVH induced by CH and longterm CIH exposure has received little attention.…”

Section: Discussionsupporting

confidence: 88%

“…The impact of caloric restriction (CR) on inducing weight loss in cardiac hypertrophy has substantial clinical importance (Karwi et al, 2019). Recently, it has been reported in both humans and animal models that overweight and obesity influence highaltitude illness outcomes such as pulmonary hypertension (San Martin et al, 2017;Brito et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

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Lower Body Weight in Rats Under Hypobaric Hypoxia Exposure Would Lead to Reduced Right Ventricular Hypertrophy and Increased AMPK Activation

et al. 2020

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Background: Both chronic hypoxia (CH) and long-term chronic intermittent hypoxia (CIH) exposure lead to right ventricular hypertrophy (RVH). Weight loss is an effective intervention to improve cardiac function and energy metabolism in cardiac hypertrophy. Likewise, caloric restriction (CR) also plays an important role in this cardioprotection through AMPK activation. We aimed to determine the influence of body weight (BW) on RVH, AMPK and related variables by comparing rats exposed to both hypoxic conditions. Methods: Sixty male adult rats were separated into two groups (n = 30 per group) according to their previous diet: a caloric restriction (CR) group and an ad libitum (AL) group. Rats in both groups were randomly assigned to 3 groups: a normoxic group (NX, n = 10), a CIH group (2 days hypoxia/2 days normoxia; n = 10) and a CH group (n = 10). The CR group was previously fed 10 g daily, and the other was fed ad libitum. Rats were exposed to simulated hypobaric hypoxia in a hypobaric chamber set to 428 Torr (the equivalent pressure to that at an altitude of 4,600 m above sea level) for 30 days. Measurements included body weight; hematocrit; serum insulin; glycemia; the degree of RVH (Fulton's index and histology); and AMPK, mTOR, and PP2C expression levels in the right ventricle determined by western blotting.Results: A lower degree of RVH, higher AMPK activation, and no activation of mTOR were found in the CR groups exposed to hypobaric hypoxia compared to the AL groups (p < 0.05). Additionally, decreased glycemia and serum insulin levels were observed. Interestingly, PP2C expression showed an increase in the AL groups but not in the CR groups (p < 0.05).Frontiers in Physiology | www.frontiersin.org 1 April 2020 | Volume 11 | Article 342Flores et al. AMPK in Long-Term Hypobaric HypoxiaConclusion: Maintaining a low weight before and during exposure to high-altitude hypoxia, during either CH or CIH, could prevent a major degree of RVH. This cardioprotection would likely be due to the activation of AMPK. Thus, body weight is a factor that might contribute to RVH at high altitudes.

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Section: Discussionsupporting

confidence: 88%

Section: Introductionmentioning

confidence: 99%

Lower Body Weight in Rats Under Hypobaric Hypoxia Exposure Would Lead to Reduced Right Ventricular Hypertrophy and Increased AMPK Activation

et al. 2020

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“…1,[7][8][9] Another important characteristic of the failing heart is the development of cardiac insulin resistance. 1,4,[10][11][12] Together, these changes impair the metabolic flexibility of the heart and its ability to adapt to different workloads. 1,4 Decreased mitochondrial ATP production results in an upregulation in glycolysis-derived cardiac ATP production in the failing heart in an attempt to compensate for the reduction in oxidative metabolism.…”

Section: Energy Metabolism In the Normal Heartmentioning

confidence: 99%

“…5 In addition, the high rates of glycolysis become uncoupled from glucose oxidation, which is impaired in heart failure due in part to a decrease in insulin-stimulation of glucose oxidation. 1,10,11 The increased reliance on glycolysis-derived ATP production leads to the production of lactate and H + as metabolic byproducts arising from glycolysis uncoupled to glucose oxidation. This compromises cardiac efficiency as ATP is redirecting ATP away from supporting contractile function and towards restoring ionic homeostasis.…”

Section: Energy Metabolism In the Normal Heartmentioning

confidence: 99%

“…1,4 Data from human and animal studies suggest that insulin-stimulated mitochondrial glucose oxidation is decreased, and that this decrease in glucose oxidation is uncoupled from high cytosolic glycolytic rates in the failing heart (Figure 1). 10,11,18 In fact, decreased cardiac glucose oxidation rates is a feature of early metabolic remodeling in heart failure and precedes cardiac dysfunction. 2,3,19 Of note, some studies suggested that glucose oxidation is increased in heart failure, but this could be driven by increased glucose uptake and subsequent high glycolytic rates in the failing heart.…”

Section: Ketone Oxidationmentioning

confidence: 99%

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Energy metabolism in patients with diabetes and heart failure

2019

Heart Metab

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The heart has a very high energy demand, which is mostly met by mitochondrial oxidative phosphorylation and, to a lesser extent, by glycolysis. In heart failure, there are substantial alterations in myocardial energy metabolism that lead to an “energy-deficient” state. This includes a marked reduction in overall mitochondrial oxidative phosphorylation and an uncoupling between high glycolysis rates and low glucose oxidation, which together contributes to the energy deficit and deteriorates contractile dysfunction. Cardiac ketone oxidation is also increased in heart failure, although it has yet to be determined whether this is an adaptive or maladaptive alteration. Diabetes is a major risk factor for heart failure development. It induces alterations in myocardial energy metabolism and is often associated with ventricular dysfunction. Similar to heart failure, a major change in myocardial energy metabolism in diabetic patients is a reduction in glucose oxidation, which negatively influences cardiac function. In both heart failure and diabetes, a growing body of evidence suggests that targeting myocardial energy metabolism by optimizing cardiac energy substrate preference could be a potential therapeutic approach to improve patient outcomes.

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U‐shaped association between body mass index and ejection fraction in intensive care unit patients with heart failure

et al. 2022

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Aims There are limited data about the relationship between body mass index (BMI) and left ventricular ejection fraction (EF) in patients with heart failure (HF). The study aims to assess the correlation between BMI and left ventricular EF under HF conditions. Methods and results We derived the data from the Dryad Digital Repository for analysis, and the information of the original patients was obtained from the MIMIC‐III database by the data uploader. We performed smooth curve and two piecewise linear regression analyses to evaluate the association between BMI and EF in HF patients. A total of 962 participants were included in this study, with age of 73.7 ± 13.5 years, and 475 participants were male (49.4%). The results of the smooth curve supported a U‐shaped relationship between BMI and EF, and the inflection point was found to be a BMI of 23.3 kg/m2 in these HF patients. After adjusting for potential confounders, we found that EF decreased with increasing BMI up to the inflection point (β = −0.7, 95% CI −1.3 to −0.1, P = 0.028), whereas beyond the turning point, the relationship between EF and BMI showed a positive correlation (β = 0.2, 95% CI 0.1–0.3 P < 0.001). Importantly, ischaemic heart disease (interaction P = 0.0499) and hyperlipidaemia (interaction P = 0.0162) affected the association between BMI and EF in the lower BMI group (BMI < 23.3 kg/m2), although only diabetes mellitus (interaction P = 0.0255) altered the association between BMI and EF in the higher BMI group (BMI ≥ 23.3 kg/m2). Conclusions In addition to higher BMI, we also found that lower BMI is related to higher EF in intensive care unit patients with HF, supporting a U‐shaped association between BMI and EF.

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Weight loss enhances cardiac energy metabolism and function in heart failure associated with obesity

Cited by 36 publications

References 50 publications

Lower Body Weight in Rats Under Hypobaric Hypoxia Exposure Would Lead to Reduced Right Ventricular Hypertrophy and Increased AMPK Activation

Lower Body Weight in Rats Under Hypobaric Hypoxia Exposure Would Lead to Reduced Right Ventricular Hypertrophy and Increased AMPK Activation

Energy metabolism in patients with diabetes and heart failure

U‐shaped association between body mass index and ejection fraction in intensive care unit patients with heart failure

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