Molecular changes in hepatic metabolism in ZDSD rats–A new polygenic rodent model of obesity, metabolic syndrome, and diabetes

Publication date: Available online 24 January 2020Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Lu Han, Stefanie Bittner, Dachuan Dong, Yuan Cortez, Alex Bittner, Jackie Chan, Meenakshi Umar, Wen-Jun Shen, Richard G. Peterson, Fredric B. Kraemer, Salman AzharAbstractIn recent years, the prevalence of obesity, metabolic syndrome and type 2 diabetes is increasing dramatically. They share pathophysiological mechanisms and often lead to cardiovascular diseases. The ZDSD rat was suggested as a new animal model to study diabetes and the metabolic syndrome. In the current study, we have further characterized metabolic and hepatic gene expression changes in ZDSD rats. Immuno-histochemical staining of insulin and glucagon on pancreas sections of ZDSD and control SD rats revealed that ZDSD rats have severe damage to their islet structures as early as 15 weeks of age. Animals were followed till they were 26 weeks old, where they exhibited obesity, hypertension, hyperglycemia, dyslipidemia, insulin resistance and diabetes. We found that gene expressions involved in glucose metabolism, lipid metabolism and amino acid metabolism were changed significantly in ZDSD rats. Elevated levels of ER stress markers correlated with the dysregulation of hepatic lipid metabolism in ZDSD rats. Key proteins participating in unfolded protein response pathways were also upregulated and likely contribute to the pathogenesis of dyslipidemia and insulin resistance. Bas...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - Category: Molecular Biology Source Type: research

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Non-alcoholic fatty liver disease (NAFLD) and chronic kidney disease (CKD) are worldwide public health problems, affecting up to 25 –30% (NAFLD), and up to 10–15% (CKD) of the general population. Recently, it has also been established that there is a strong association between NAFLD and CKD, regardless of the presence of potential confounding diseases such as obesity, hypertension and type 2 diabetes. Since NAFLD and CKD are both common diseases that often occur alongside other metabolic conditions, such as type 2 diabetes or metabolic syndrome, elucidating the relative impact of NAFLD on the risk of incident C...
Source: Journal of Hepatology - Category: Gastroenterology Authors: Tags: Review Source Type: research
Metabolic syndrome (MetS) is a pathologic condition that encompasses dyslipidaemia, abdominal obesity, insulin resistance, and hypertension [1] and is strongly linked to increasing incidence of chronic diseases, including type 2 diabetes, cancer, cardiovascular disease, chronic kidney disease and chronic obstructive pulmonary disease [2 –4]. The global epidemic of MetS underscores the vital need for more attention to be paid to the prevention and treatment MetS by controlling lifestyles and environmental factors such as manipulation of macro- and micronutrients in dietary patterns, including branch chain amino acids ...
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Abstract Metabolic surgery is increasingly becoming recognized as a more effective treatment for patients with type 2 diabetes (T2D) and obesity as compared to lifestyle modification and medical management alone. Both observational studies and clinical trials have shown metabolic surgery to result in sustained weight loss (20-30%), T2D remission rates ranging from 23% to 60%, and improvement in cardiovascular risk factors such as hypertension and dyslipidemia. Metabolic surgery is cost-effective and relatively safe, with perioperative risks and mortality comparable to low-risk procedures such as cholecystectomy, h...
Source: Annual Review of Medicine - Category: General Medicine Authors: Tags: Annu Rev Med Source Type: research
ConclusionsPrevalence of both obesity and metabolic syndrome is increasing in alcoholic liver disease patients. Further studies are required to investigate effective interventions to avoid disease progression in these high-risk patients.
Source: Digestive Diseases and Sciences - Category: Gastroenterology Source Type: research
Metabolic syndrome (MetS) is a public health problem of great impact and significance. MetS is generally defined as a grouping of abdominal obesity, impaired glucose metabolism, dyslipidemia and hypertension and has an estimated national prevalence of approximately 34% [1,2]. The presence of MetS has been previously found to confer numerous adverse long-term health consequences, including an increased risk for cardiovascular disease, the development of type 2 diabetes mellitus, fatty liver disease and cancer [3 –6].
Source: International Journal of Cardiology - Category: Cardiology Authors: Source Type: research
Authors: Khaing P, Pandit P, Awsare B, Summer R Abstract Obesity, diabetes mellitus, and the metabolic syndrome are important risk factors for the development of cardiovascular disease, with significant impact on human morbidity and mortality. Several decades of research have accumulated considerable knowledge about the mechanisms by which metabolic conditions precipitate systemic cardiovascular diseases. In short, these mechanisms are thought to involve changes in the external environment of vascular cells, which are mediated by the pro-inflammatory effects of adipokines, free fatty acids, and hyperglycemia. Thus,...
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Source: Obesity Research and Clinical Practice - Category: Eating Disorders & Weight Management Source Type: research
ConclusionsConsistent with existing clinical practice guidelines, which recommend lifestyle intervention and treatment for comorbidities related to fatty liver disease as first-line treatment, trial evidence supports the efficacy of some diabetes drugs (especially pioglitazone) in patients with NAFLD or NASH, though weight gain with some diabetes drugs may warrant caution. Larger trials are needed to better characterize the efficacy and harms of diabetes pharmacotherapy in these patients.
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Source: Expert Review of Cardiovascular Therapy - Category: Cardiology Tags: Expert Rev Cardiovasc Ther Source Type: research
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