Effects of obesity and diabesity on heart rhythm in the Zucker rat

Sultan, Ahmed; Jacobson, Michael; Adeghate, Ernest; Oulhaj, Abderrahim; Shafiullah, Mohamed; Qureshi, Anwar; Howarth, Frank Christopher

doi:10.1111/1440-1681.13473

Cited by 5 publications

(4 citation statements)

References 61 publications

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“…Finally, gap junction protein Connexin Cx45 is important for electrical signal conduction between cardiac myocytes and heart rhythm [ 51 ]. In this experiment, the expression of Cx45 was reduced in ZF and modestly reduced in ZDF compared to ZL ventricle tissue, which may have implications for disturbances in heart rhythm, which have been reported in a previous study [ 52 ]. Interestingly, it has been reported that mRNA expression levels for Gja7 (Cx45) was significantly increased in SAN from diabetic heart compared to controls [ 53 ].…”

Section: Discussionsupporting

confidence: 76%

Effects of Obesity and Diabesity on Ventricular Muscle Structure and Function in the Zucker Rat

Sultan

Adeghate

Emerald

et al. 2022

Life

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(1) Background: Cardiovascular complications are a leading cause of morbidity and mortality in diabetic patients. The effects of obesity and diabesity on the function and structure of ventricular myocytes in the Zucker fatty (ZF) rat and the Zucker diabetic fatty (ZDF) rat compared to Zucker lean (ZL) control rats have been investigated. (2) Methods: Shortening and intracellular Ca2+ were simultaneously measured with cell imaging and fluorescence photometry, respectively. Ventricular muscle protein expression and structure were investigated with Western blot and electron microscopy, respectively. (3) Results: The amplitude of shortening was increased in ZF compared to ZL but not compared to ZDF myocytes. Resting Ca2+ was increased in ZDF compared to ZL myocytes. Time to half decay of the Ca2+ transient was prolonged in ZDF compared to ZL and was reduced in ZF compared to ZL myocytes. Changes in expression of proteins associated with cardiac muscle contraction are presented. Structurally, there were reductions in sarcomere length in ZDF and ZF compared to ZL and reductions in mitochondria count in ZF compared to ZDF and ZL myocytes. (4) Conclusions: Alterations in ventricular muscle proteins and structure may partly underlie the defects observed in Ca2+ signaling in ZDF and ZF compared to ZL rat hearts.

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Section: Discussionsupporting

confidence: 76%

Effects of Obesity and Diabesity on Ventricular Muscle Structure and Function in the Zucker Rat

Sultan

Adeghate

Emerald

et al. 2022

Life

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“…In conclusion, increased neuronal activation in sympathoexcitatory brain regions has been demonstrated for the first time in an animal others. 67,68 Current therapies that target sympathoexcitation in type 2 DM have reduced effectiveness compared to non-DM individuals. 4 Our findings suggest that pharmacotherapies 5 targeting the central source of cardiac sympathoexcitation in type 2 DM might be an alternative treatment strategy.…”

Section: Discussionmentioning

confidence: 99%

Increased neuronal activation in sympathoregulatory regions of the brain and spinal cord in type 2 diabetic rats

Sethi

Augustine

Bouwer

et al. 2021

J Neuroendocrinology

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Increased cardiac sympathetic nerve activity in type 2 diabetes mellitus (DM) suggests impaired autonomic control of the heart. However, the central regions that contribute to the autonomic cardiac pathologies in type 2 DM are unknown. Therefore, we tested the hypothesis that neuronal activation would be increased in central sympathoregulatory areas in a pre-clinical type 2 DM animal model. Immunohistochemistry in 20-week-old male Zucker diabetic fatty (ZDF) rats revealed an increased number of neurones expressing ΔFosB (a marker of chronic neuronal activation) in the intermediolateral column (IML) of the spinal cord in DM compared to non-diabetic (non-DM) rats (P < 0.05). Rostral ventrolateral medulla (RVLM) neurones activate IML neurones and receive inputs from the hypothalamic paraventricular nucleus (PVN), as well as the nucleus tractus solitarius (NTS) and area postrema (AP), in the brainstem.We observed more ΔFosB-positive noradrenergic RVLM neurones (P < 0.001) and corticotrophin-releasing hormone PVN neurones (P < 0.05) in DM compared to non-DM rats. More ΔFosB-positive neurones were also observed in the NTS (P < 0.05) and AP (P < 0.01) of DM rats compared to non-DM rats. Finally, because DM ZDF rats are obese, we also expected increased activation of pro-opiomelanocortin (POMC) arcuate nucleus (ARC) neurones in DM rats; however, fewer ΔFosB-positive POMC ARC neurones were observed in DM compared to non-DM rats (P < 0.01). In conclusion, increased neuronal activation in the IML of type 2 DM ZDF rats might be driven by RVLM neurones that are possibly activated by PVN, NTS and AP inputs.Elucidating the contribution of central sympathoexcitatory drive in type 2 DM might improve the effectiveness of pharmacotherapies for diabetic heart disease.

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“…Recent in vivo biotelemetry experiments have demonstrated that HR was significantly reduced in ZDF compared to ZF and ZL control rats in the absence of changes in body temperature and physical activity [47]. Age related changes in PQ intervals, QRS intervals, QT and QTc intervals between different groups were also reported.…”

Section: Electrical Conduction System Of the Heart And Obesitymentioning

confidence: 92%

Cellular and Molecular Effects of Obesity on the Heart

Sultan

Singh

Howarth

2021

Cellular and Biochemical Mechanisms of Obesity

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Obesity is a serious chronic disease that is responsible for a large number of deaths worldwide. The Body Mass Index (BMI) is widely used to provide definitions of overweight and obesity. A BMI of 20-24 is considered normal, a BMI of 25-29 is considered overweight and a BMI of 30 and over is considered obese. Overweight and obesity are attributed to a variety of risk factors including smoking, genetics, alcohol consumption, high level of stress, physical inactivity, unhealthy diet containing excessive amounts of fat and sugar, food snacking and binging, low calorie expenditure, socio-economic and psychological issues and some medications. Overweight and obesity are also associated with various illnesses including hormonal imbalance, hypothyroidism, insulin resistance (IR), polycystic ovary syndrome and Cushing's syndrome. Obesity is a risk factor for diabetes (diabesity) resulting in hyperglycemia which enhances the generation of reactive carbonyl species (RCS) and reactive oxygen species (ROS) in the myocardium. Both ROS and RCS elicit insults to cardiac muscle which may result in apoptosis, fibrosis, hypertrophy, mitochondrial dysfunction, derangement in cellular calcium homeostasis and electrical signaling. In response to these insults the heart goes through a process of remodeling in order to maintain the demands of the body. Over time there may be development of cardiomyopathy, reduced ejection fraction and perhaps arrhythmias and sudden cardiac death (SCD). In general obesity is a preventable illness. This review describes the cellular and molecular effects of obesity on the heart leading to SCD.

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Effects of obesity and diabesity on heart rhythm in the Zucker rat

Cited by 5 publications

References 61 publications

Effects of Obesity and Diabesity on Ventricular Muscle Structure and Function in the Zucker Rat

Effects of Obesity and Diabesity on Ventricular Muscle Structure and Function in the Zucker Rat

Increased neuronal activation in sympathoregulatory regions of the brain and spinal cord in type 2 diabetic rats

Cellular and Molecular Effects of Obesity on the Heart

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