The Power of the Heterogeneous Stock Rat Founder Strains in Modeling Metabolic Disease. Endocrinology 2023 Nov 02;164(12)
Date
10/26/2023Pubmed ID
37882530Pubmed Central ID
PMC10637104DOI
10.1210/endocr/bqad157Scopus ID
2-s2.0-85176509096 (requires institutional sign-in at Scopus site)Abstract
Metabolic diseases are a host of complex conditions, including obesity, diabetes mellitus, and metabolic syndrome. Endocrine control systems (eg, adrenals, thyroid, gonads) are causally linked to metabolic health outcomes. N/NIH Heterogeneous Stock (HS) rats are a genetically heterogeneous outbred population developed for genetic studies of complex traits. Genetic mapping studies in adult HS rats identified loci associated with cardiometabolic risks, such as glucose intolerance, insulin resistance, and increased body mass index. This study determined underappreciated metabolic health traits and the associated endocrine glands within available substrains of the HS rat founders. We hypothesize that the genetic diversity of the HS rat founder strains causes a range of endocrine health conditions contributing to the diversity of cardiometabolic disease risks. ACI/EurMcwi, BN/NHsdMcwi, BUF/MnaMcwi, F344/StmMcwi, M520/NRrrcMcwi, and WKY/NCrl rats of both sexes were studied from birth until 13 weeks of age. Birth weight was recorded, body weight was measured weekly, metabolic characteristics were assessed, and blood and tissues were collected. Our data show wide variation in endocrine traits and metabolic health states in ACI, BN, BUF, F344, M520, and WKY rat strains. This is the first report to compare birth weight, resting metabolic rate, endocrine gland weight, hypothalamic-pituitary-thyroid axis hormones, and brown adipose tissue weight in these rat strains. Importantly, this work unveils new potential for the HS rat population to model early life adversity and adrenal and thyroid pathophysiology. The HS population likely inherited risk alleles for these strain-specific traits, making the HS rat a powerful model to investigate interventions on endocrine and metabolic health.
Author List
Wagner VA, Holl KL, Clark KC, Reho JJ, Lehmler HJ, Wang K, Grobe JL, Dwinell MR, Raff H, Kwitek AEAuthors
Karen C. Clark Research Scientist I in the Physiology department at Medical College of WisconsinMelinda R. Dwinell PhD Professor in the Physiology department at Medical College of Wisconsin
Justin L. Grobe PhD Professor in the Physiology department at Medical College of Wisconsin
Anne E. Kwitek PhD Professor in the Physiology department at Medical College of Wisconsin
Hershel Raff PhD Professor in the Academic Affairs department at Medical College of Wisconsin
John J. Reho Research Scientist II in the Physiology department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
AnimalsBirth Weight
Female
Insulin Resistance
Male
Rats
Rats, Inbred ACI
Rats, Inbred BUF
Rats, Inbred F344
Rats, Inbred WKY
