Phenotypic and genotypic changes in obesity and type 2 diabetes of male KK mice with aging

Abstract

Research into the prevention and treatment of age-related metabolic diseases are important in the present-day situation of the aging population. We propose that an elderly diabetic mouse model may be useful to such research as it exhibits deterioration of glucose and lipid metabolism. Although the KK mouse strain is commonly used as a model of moderate obesity and type 2 diabetes, the utility of this strain as an elderly obese and diabetic model mouse for research into aging remains unclear. The present study aimed to investigate age-related changes of glucose and lipid metabolism in male KK mice fed a standard chow diet.We demonstrate that 40 weeks KK mice exhibit age-related dysfunctions, such as development of insulin resistance associated with pancreatic islet hypertrophy and decreased lipolysis in white adipose tissue (WAT) compared with 15 weeks KK mice. However, aging does not appear to cause mitochondrial dysfunction of brown adipose tissue. Unexpectedly, hyperglycemia, potential glucose uptake in insulin-sensitive organs, hepatic lipid accumulation, hypertrophy of adipocytes, and inflammation in epididymal WAT did not worsen but rather compensated in 40 weeks KK mice. Our data indicate that the use of male KK mice as an elderly obese and diabetic mouse model has some limitations and in order to represent a useful elderly obese and diabetic animal model, it may be necessary to induce deterioration of glucose and lipid metabolism in KK mice through breeding with high-sucrose or high-fat diets.

Finding a Link between Obesity and Senescence: A Systematic Review and Meta-Analysis

“…The data extracted from the three studies varied for the animal study by Rabhi et al, the extracted data were fibrotic stromal microenvironment; ECM production; PDGFRα and PDGFRβ; Osteopontin production; senescent CD9+ ( 23 ). While the study by Iizuka et al took data in the form of Blood glucose; plasma insulin and HOMA-IR; oxidative stress (d-ROMS); hepatic triglycerides; morphology islets; GLUT4 expressions; Mitochondria UCP1 ( 24 ). tissue-based study conducted by Frasca et al took data in the form of Expression of SASP Markers in B Cells; B cells count (memory and naive B cells); glucose and lipid uptake of B cells ( 25 ).…”

Animal models for type 1 and type 2 diabetes: advantages and limitations

“…The KK mice have been useful in discovering novel treatments to improve insulin resistance ( 27 ). Some drawbacks for using this mouse model to study diabetes include its high expense, limited availability, and its possible genetic variations between individual mice due to its non-homogenous genetic nature ( 71 , 105 ).…”

RNA-Seq analysis of obese <i>Pdha1^fl/fl</i>Lyz2-Cre mice induced by a high-fat diet

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