High Energy Intake Induced Overexpression of Transcription Factors and Its Regulatory Genes Involved in Acceleration of Hepatic Lipogenesis: A Rat Model for Type 2 Diabetes.

Suresh P Khadke,Aniket A Kuvalekar,Nitin Mantri,Abhay M Harsulkar

doi:10.3390/biomedicines7040076

Suresh P Khadke, Aniket A Kuvalekar + Show 2 more

Open Access

https://doi.org/10.3390/biomedicines7040076

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Abstract

Type 2 diabetes mellitus (T2DM) is a metabolic disorder characterized by impaired insulin action and its secretion. The objectives of the present study were to establish an economical and efficient animal model, mimicking pathophysiology of human T2DM to understand probable molecular mechanisms in context with lipid metabolism. In the present study, male Wistar rats were randomly divided into three groups. Animals were fed with high fat diet (HFD) except healthy control (HC) for 12 weeks. After eight weeks, intra peritoneal glucose tolerance test was performed. After confirmation of glucose intolerance, diabetic control (DC) group was injected with streptozotocin (STZ) (35 mg/kg b.w., i.p.). HFD fed rats showed increase (p ≤ 0.001) in glucose tolerance and HOMA-IR as compared to HC. Diabetes rats showed abnormal (p ≤ 0.001) lipid profile as compared to HC. The hepatocyte expression of transcription factors SREBP-1c and NFκβ, and their target genes were found to be upregulated, while PPAR-γ, CPT1A and FABP expressions were downregulated as compared to the HC. A number of animal models have been raised for studying T2DM, but the study has been restricted to only the biochemical level. The model is validated at biochemical, molecular and histopathological levels, which can be used for screening new therapeutics for the effective management of T2DM.

Highlights

Non-communicable diseases (NCDs), known as chronic diseases, result from a combination of genetic, physiological, environmental and lifestyle factors
The glucose intolerance was successfully developed at 30% lard oil diet
Insulin resistance contributes to the characteristic dyslipidemia associated with Type 2 diabetes mellitus (T2DM) [10] which is linked with significant cardiovascular incidences [10]

Summary

Introduction

Non-communicable diseases (NCDs), known as chronic diseases, result from a combination of genetic, physiological, environmental and lifestyle factors. Among all NCDs, Type 2 diabetes (T2DM) is the most common which accounts for 90% of all forms of diabetes with a rapidly rising prevalence globally. Around half of diabetics are undiagnosed which results in uncontrolled diabetes and further increase in the global burden of diabetes [2,3,4]. NCDs are one of the major public health challenges of the 21st century, associated with elevated economic burden especially in low- and middle-income countries. Social and economic costs of NCDs continue to escalate at an overwhelming rate and will soon exceed the capabilities of countries to address and manage the burden of these conditions [5]

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