Journal article
The power of the Heterogenous Stock rat founder strains in modeling metabolic disease
Endocrinology (Philadelphia), Vol.164(12), pp.1-19
11/02/2023
DOI: 10.1210/endocr/bqad157
PMCID: PMC10637104
PMID: 37882530
Abstract
Metabolic diseases are a host of complex conditions, including obesity, diabetes mellitus, and metabolic syndrome. Endocrine control systems (e.g., 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 BMI. 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.
Details
- Title: Subtitle
- The power of the Heterogenous Stock rat founder strains in modeling metabolic disease
- Creators
- Valerie A Wagner - Medical College of WisconsinKatie L HollKaren C Clark - Medical College of WisconsinJohn J Reho - Medical College of WisconsinHans-Joachim Lehmler - University of Iowa, Occupational and Environmental HealthKai Wang - University of Iowa, BiostatisticsJustin L Grobe - Medical College of WisconsinMelinda R Dwinell - Medical College of WisconsinHershel Raff - Medical College of WisconsinAnne E Kwitek - Medical College of Wisconsin
- Resource Type
- Journal article
- Publication Details
- Endocrinology (Philadelphia), Vol.164(12), pp.1-19
- DOI
- 10.1210/endocr/bqad157
- PMID
- 37882530
- PMCID
- PMC10637104
- NLM abbreviation
- Endocrinology
- eISSN
- 1945-7170
- Publisher
- Oxford University Press
- Grant note
- name: University of Iowa Environmental Health Sciences Research Center, award: P30ES005605; name: National Institutes of Health Predoctoral Training, award: T32GM008629; DOI: 10.13039/100000002, name: National Institutes of Health, award: R01HL134850, R01DK133121, P01HL084207, R01HL064541, P01HL149620, U24HG010859, U24HG010423; name: Hybrid Rat Diversity Panel, award: R24OD024617; DOI: 10.13039/100013762, name: Advocate Aurora Research Institute; DOI: 10.13039/100008980, name: Medical College of Wisconsin
- Language
- English
- Electronic publication date
- 10/26/2023
- Date published
- 11/02/2023
- Academic Unit
- Occupational and Environmental Health; Iowa Neuroscience Institute; Biostatistics
- Record Identifier
- 9984473205402771
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