Cotton rat (Sigmodon hispidus) develops metabolic disorders associated with visceral adipose inflammation and fatty pancreas without obesity
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Obesity induces metabolic disorders such as type 2 diabetes, hypertension, and cardiovascular diseases and has become a global health concern. Recent studies imply that fat accumulation in nonadipose tissue correlates with metabolic disorders. However, there are no suitable animal models to evaluate this phenomenon. This study investigated the characteristics of metabolic disorders found in cotton rat (Sigmodon hispidus). Blood biochemical examinations revealed that cotton rats, predominantly males, developed hyperinsulinemia, hyperglycemia, and dyslipidemia when fed a normal diet. The islets increased in size through β-cell hyperplasia, which was associated with serum insulin level in both sexes, strongly indicating insulin resistance. In male cotton rats, oxidative stress was observed in β cells, and macrophage infiltration into the visceral white adipose tissue was reported, both of which were associated with serum insulin level without visceral obesity. In contrast, female cotton rats developed hyperinsulinemia without histopathological changes that were reported in males. Adipocytes were found to be accumulated in the pancreas but not in the liver of both sexes during aging. Pancreatic fat accumulation was associated with the serum insulin level only in females. Taken together, cotton rats developed metabolic disorders associated with visceral fat inflammation in the absence of obesity. In addition, pancreatic ectopic fat may also be related to the early stages of these conditions. Thus, the cotton rat may serve as a novel and useful model for metabolic disorders characterized by visceral adipose inflammation and ectopic fat accumulation in the pancreas without obesity.
KeywordsCotton rat Ectopic fat Metabolic disorder Obesity Visceral fat inflammation
We would like to acknowledge Daisuke Nakamura, Saori Nakamura, Shinobu Sato, and Keisuke Yokoyama in Sankyo Labo Service Corporation, Inc., Sapporo, Hokkaido, Japan, for their assistance in the animal experiments.
This work was partially supported by JSPS KAKENHI Grant Number JP18K0703708.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
All procedures performed in studies involving animals were in accordance with the ethical standards of Hokkaido Institute of Public Health (approval No. K27-03). This article does not contain any studies with human participants performed by any of the authors.
- Faith RE, Montgomery CA, Durfee WJ, Aguilar-Cordova E, Wyde PR (1997) The cotton rat in biomedical research. Lab Anim Sci 47:337–345Google Scholar
- Gu D, Sarvetnick N (1993) Epithelial cell proliferation and islet neogenesis in IFN-gamma transgenic mice. Development 118:33–46Google Scholar
- Kanda Y, Shimoda M, Hamamoto S, Tawaramoto K, Kawasaki F, Hashiramoto M, Nakashima K, Matsuki M, Kaku K (2010) Molecular mechanism by which pioglitazone preserves pancreatic β-cells in obese diabetic mice: evidence for acute and chronic actions as a PPARγ agonist. Am J Physiol Endocrinol Metab 298:E278–E286CrossRefGoogle Scholar
- Nakamura T, Ichii O, Irie T, Mizoguchi T, Shinohara A, Kouguchi H, Sunden Y, Otsuka-Kanazawa S, Elewa YHA, Koshimoto C, Nagasaki KI, Kon Y (2018) Cotton rats (Sigmodon hispidus) possess pharyngeal pouch remnants originating from different primordia. Histol Histopathol 33:555–565Google Scholar
- Nolte T, Brander-Weber P, Dangler C, Deschl U, Elwell MR, Greaves P, Hailey R, Leach MW, Pandiri AR, Rogers A, Shackelford CC, Spencer A, Tanaka T, Ward JM (2016) Nonproliferative and proliferative lesions of the gastrointestinal tract, pancreas and salivary glands of the rat and mouse. J Toxicol Pathol 29:1S–125SCrossRefGoogle Scholar
- Tajima S, Horiuchi S (1989) Biological reference data book on experimental animals, 1st ed (Japanese). Soft Science, TokyoGoogle Scholar
- Waldum HL, Rørvik H, Falkmer S, Kawase S (1999) Neuroendocrine (ECL cell) differentiation of spontaneous gastric carcinomas of cotton rats (Sigmodon hispidus). Lab Anim Sci 49:241–247Google Scholar
- Yao L, Herlea-Pana O, Heuser-Baker J, Chen Y, Barlic-Dicen J (2014) Roles of the chemokine system in development of obesity, insulin resistance, and cardiovascular disease. J Immunol Res 181450Google Scholar