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Preliminary evidence shows that obesity may lead to renal inflammation and an unbalanced renal tissue lipidic profile, particularly after menopause.

Obesity is a risk factor for chronic kidney disease (CKD). However, the prevalence of CKD has not increased in parallel with the obesity pandemic. It is important to identify the patients in whom obesity induces renal damage. Menopause can promote kidney disease in obese women, but the interaction is unclear. 

A previous study showed that obese male and female mice developed glomerular hyperfiltration, albuminuria, and glomerulomegaly, with more severe changes noted in the ovariectomized females. A recent study by the same researchers, published in the International Journal of Molecular Sciences, evaluated renal inflammation and lipotoxicity in male and female obese mice in relation to obesity and menopause.

Inflammatory Marker Expression in Relation to Obesity and Dietary Variation

Obese male mice had increased expression of all inflammatory markers evaluated in the renal cortex, including NF-κβ-p65, IL-1β, MCP-1, and TNF-α.

Female mice on a high-fat diet (HFD) had higher NF-κβ-p65, MCP-1, and TNF-α expression in the renal cortex than those on a standard diet (SD). Obese ovariectomized mice had an increased expression of inflammatory markers IL-1β and TNF-α compared to non-ovariectomized females on HFD and higher levels of IL-1β, TNF-α, and MCP-1 compared to ovariectomized mice on SD.

Gender and Obesity in Renal Tissue Inflammation and Lipidomic Profiling

In males, total lipid content in the renal tissue was higher in those on HFD than those on SD. No such differences were found in females. Major lipid class proportions were comparable in all groups.

Obese mice showed an imbalanced lipidomic profile with lower pro-inflammatory and higher anti-inflammatory fatty acid proportions. Renal tissue of obese animals exhibited lower 16:0, 16:1 n-7, 18:2 n-6, and 20:3 n-6 levels and higher 20:2 n-6 and 22:6 n-3 levels. These pro/ anti-inflammatory profile responses were similarly observed in the major phospholipids phosphatidylcholine (PC) and phosphatidylethanolamine (PE). Some of these changes were different in obese ovariectomized females, particularly fatty acid profiles of specific lipid classes, with lower 16:0 and 16:1 n-7 in triglycerides (TAG) but higher 18:0 in TAG and PC levels and a higher content of the PE plasmalogen 18:0 DMA. The levels of 22:6 n-3 in PC and PE were lower in obese ovariectomized mice, suggesting an impaired anti-inflammatory response.

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Correlation Between Lipidomic Analysis of Urine and Renal Tissue Findings

The results of lipidomic analysis of fatty acids in urine resembled those of the renal tissue in some aspects, such as higher 22:6 n-3 levels in obese males and females. Higher urinary levels of some phospholipids such as PC, cholesterol, and phosphatidylinositol were also observed in obese males and females, which may indicate the presence of renal cells in urine.

In conclusion, obesity-related renal disease may comprise renal inflammation and lipotoxicity, which, in this animal study, were more prominent in obese animals after menopause. However, the interaction with menopause needs further investigation.

Source:

Afonso-Alí, A., Porrini, E., Teixido-Trujillo, S., Pérez-Pérez, J. A., Luis-Lima, S., Acosta-González, N. G., Sosa-Paz, I., Díaz-Martín, L., Rodríguez-González, C., & Rodríguez-Rodríguez, A. E. (2023). The Role of Gender Differences and Menopause in Obesity-Related Renal Disease, Renal Inflammation and Lipotoxicity. International journal of molecular sciences, 24(16), 12984. https://doi.org/10.3390/ijms241612984