The Influence of Sex on Early Stage Markers of Kidney Dysfunction in Response to Juvenile Obesity
Open accessAbstract
Changes within the kidney in response to obesity are critical in determining the magnitude of later dysfunction. However, the cause of this process in response to juvenile onset obesity and how it can be determined by sex is poorly understood. We therefore examined the effect of juvenile obesity induced by exposure to a restricted activity environment from weaning until early adulthood on the molecular responses within the kidney together with glomerular area and nucleated cell number. This was stratified by sex and was undertaken in a sheep model of early obesity. Despite a similar magnitude of increase in fat mass with obesity onset between sexes, adverse effects on glomerular area and cell number together with raised gene expression within the kidney only occurred in males. Irrespective of obesity, gene expression of C-C motif receptor 2 was higher, and interleukin-6 lower, in male kidneys compared with female kidneys. The effects of sex on molecular differences within the kidney were amplified with obesity, which had no effect on any gene studied in females but had an enhanced response in males. Obese males therefore showed increased gene expression of a range of markers relating to the glucocorticoid axis, inflammation, and lipid sensing. In conclusion, young females were protected from adverse renal effects of obesity, which results in very little inflammatory or related responses. Our findings emphasize the critical importance of sex specificity in disease pathogenesis. An increased understanding of the specific mechanisms will have important implications for therapeutic strategies aimed at preventing adverse consequences of obesity.
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Sex appears to influence the development of renal changes in obesity.
“Interestingly, sex appears to influence the development of renal changes in obesity.”
From Obesity-Associated Hypertension: Recent Progress in Deciphering the Pathogenesis (2014) · cites this paper as [67]
Female sheep are protected from adverse renal effects caused by obesity despite exhibiting similar metabolic and cardiovascular phenotypes as the male counterparts.
“This is based on the observation that female sheep are protected from adverse renal effects caused by obesity despite exhibiting similar metabolic and cardiovascular phenotypes as the male counterparts (67).”
From Obesity-Associated Hypertension: Recent Progress in Deciphering the Pathogenesis (2014) · cites this paper as [67]
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- Authors
- Bloor, I. D., Sebert, S. P., Mahajan, R. P., & Symonds, M. E.
- Affiliations
- Queen's Medical Centre (GB)
- Venue
- Hypertension
- Published
- 2012-10
- Volume
- 60
- Issue
- 4
- Pages
- 991-997
- ISSN
- 0194-911X (ISSN-L)
- 1524-4563
- OpenAlex
- W2099288333
- Cited by
- 18
- References
- 46
- Citations by year
- 2024: 1 · 2021: 2 · 2020: 1 · 2019: 3 · 2018: 2 · 2017: 1 · 2016: 1 · 2015: 2 · 2014: 3 · 2013: 2
- FWCI
- 1.77
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Hypertension (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Wellcome Trust
- European Commission (FOOD-CT-2005)
- Royal College of Anaesthetists
- Topics
- Health Sciences › Medicine › Nephrology › Chronic Kidney Disease and Diabetes
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Birth, Development, and Health
- Keywords
- youth obesity, sex differences, renal dysfunction, glomerular area, renal gene expression, CCR2, interleukin-6, inflammation, lipid sensing, sheep model, fat mass
- MeSH terms
- Animals, Body Weight, Disease Models, Animal, Female, Kidney, Male, Obesity, Sex Factors, Sheep, Lipid Peroxidation, Interleukin-6, Gene Expression
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