Aged Monkeys Fed a High-Fat/High-Sugar Diet Recapitulate Metabolic Disorders and Cardiac Contractile Dysfunction

Zheng, Shuang; Tan, Weijiang; Li, Xiang; Li, Binglin; Gong, Baoyong; Pyle, W. Glen; Wu, Jian; Li, Lei; Luo, Ting; Zou, Yunzeng; Yang, Feng; Backx, Peter H.

doi:10.1007/s12265-021-10105-z

Cited by 13 publications

(17 citation statements)

References 67 publications

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“…Myofilament phosphorylation levels were analyzed to examine their responses to chronic pressure overload. Myofilaments were extracted as previously described, with modifications ( 19 – 21 ). The hearts were homogenized in an ice-cold cell lysis buffer comprising 60 mM KCl, 30 mM imidazole (pH 7.0), 2 mM MgCl 2 , and proteinase inhibitors, and then centrifuged at 12,000 × g at 4°C for 15 min.…”

Section: Methodsmentioning

confidence: 99%

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A Porcine Model of Heart Failure With Preserved Ejection Fraction Induced by Chronic Pressure Overload Characterized by Cardiac Fibrosis and Remodeling

Tan

Zheng

et al. 2021

Front. Cardiovasc. Med.

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Heart failure is induced by multiple pathological mechanisms, and current therapies are ineffective against heart failure with preserved ejection fraction (HFpEF). As there are limited animal models of HFpEF, its underlying mechanisms have not yet been elucidated. Here, we employed the descending aortic constriction (DAC) technique to induce chronic pressure overload in the left ventricles of Tibetan minipigs for 12 weeks. Cardiac function, pathological and cellular changes, fibrotic signaling activation, and gene expression profiles were explored. The left ventricles developed concentric hypertrophy from weeks 4 to 6 and transition to dilation starting in week 10. Notably, the left ventricular ejection fraction was maintained at >50% in the DAC group during the 12-week period. Pathological examination, biochemical analyses, and gene profile analysis revealed evidence of inflammation, fibrosis, cell death, and myofilament dephosphorylation in the myocardium of HFpEF model animals, together with gene expression shifts promoting cardiac remodeling and downregulating metabolic pathways. Furthermore, we noted the activation of several signaling proteins that impact cardiac fibrosis and remodeling, including transforming growth factor-β/SMAD family members 2/3, type I/III/V collagens, phosphatidylinositol 3-kinase, extracellular signal-regulated kinase, matrix metalloproteinases 2 and 9, tissue inhibitor of metalloproteinases 1 and 2, interleukins 6 and 1β, and inhibitor of κBα/nuclear factor-κB. Our findings demonstrate that this chronic pressure overload-induced porcine HFpEF model is a powerful tool to elucidate the mechanisms of this disease and translate preclinical findings.

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Section: Methodsmentioning

confidence: 99%

Section: Myofilament Phosphorylationmentioning

confidence: 99%

A Porcine Model of Heart Failure With Preserved Ejection Fraction Induced by Chronic Pressure Overload Characterized by Cardiac Fibrosis and Remodeling

Tan

Zheng

et al. 2021

Front. Cardiovasc. Med.

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“…The recent study established an aged monkey model with HFSD feeding, which is characterized with metabolic disorders and cardiac contractile dysfunction [1]. This is similar to that seen in the human condition.…”

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confidence: 61%

“…In a recent study, Zheng et al identified novel changes in the metabolism, cardiac morphology, and cardiac function of aged Cynomolgus monkeys fed a HSFD [1]. The HFSD caused metabolic abnormalities and cardiac contractile dysfunction in aged monkeys.…”

mentioning

confidence: 99%

“…Taken together, the recent study used the aged Cynomolgus monkeys to model HFSD-induced metabolic and cardiac dysfunction, provides a powerful model for the human condition [1]. It would be interesting to know the role of specific metabolites playing in the progress of the agerelated cardio-metabolic disorders, or to identify new biomarkers for metabolic heart diseases in elderly.…”

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confidence: 99%

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High-Fat/High-Sugar Diet Causes Metabolic Disorders and Cardiac Dysfunction: a New Model in Primates

Qiu

Xiao

2021

J. of Cardiovasc. Trans. Res.

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Multiple time‐dependent pathophysiological changes in a rabbit model of high‐fat diet‐induced hyperlipidemia

et al. 2023

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High‐fat diets (HFD) adversely affect organ systems. Several studies have examined HFD‐related disorders in animals but only in a few organs and time points. Herein, we evaluated disease development with time‐dependent HFD‐induced pathological, cardiovascular, and morphological changes in rabbits with lipid metabolism similar to that in humans for 9 weeks. The body weights and waist ratio of the HFD group were higher than those in the control group. HFD significantly increased the total cholesterol, low‐density lipoprotein, high‐density lipoprotein, and phospholipid levels after 3 weeks. Liver enzyme levels increased with hepatomegaly, steatosis, and fibrosis after 3 or 6 weeks. RBCs and hemoglobin decreased, while platelets increased in the HFD group with atherosclerosis and inflammatory cell infiltration in the aorta after 6 weeks. Ejection fraction and fractional shortening values decreased in the HFD group after 9 weeks. Creatinine increased with glomerulosclerosis in the kidneys of the HFD groups after 3 weeks, indicating renal dysfunction. Lipid accumulation was found in the pancreas after 9 weeks. Lipid accumulation and hypertrophy were observed in the adrenal glands after 3 weeks. Overall, our findings provide global reference data on the time‐dependent effects of HFD on the body and may serve as a guide for future HFD risk prevention.

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Aged Monkeys Fed a High-Fat/High-Sugar Diet Recapitulate Metabolic Disorders and Cardiac Contractile Dysfunction

Cited by 13 publications

References 67 publications

A Porcine Model of Heart Failure With Preserved Ejection Fraction Induced by Chronic Pressure Overload Characterized by Cardiac Fibrosis and Remodeling

A Porcine Model of Heart Failure With Preserved Ejection Fraction Induced by Chronic Pressure Overload Characterized by Cardiac Fibrosis and Remodeling

High-Fat/High-Sugar Diet Causes Metabolic Disorders and Cardiac Dysfunction: a New Model in Primates

Multiple time‐dependent pathophysiological changes in a rabbit model of high‐fat diet‐induced hyperlipidemia

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