Overexpression of kidney androgen-regulated protein (KAP) in the kidney prevents weight gain from eating a high-fat diet.
A study led by Dr. Anna Meseguer, head of the CIBBIM-Nanomedicine group Renal Physiopathology of the Vall Research Institute d´Hebron (VHIR) has demonstrated the role of the KAP protein in the control of the development of the metabolic syndrome produced by the ingestion of a diet rich in fat. The generation of a transgenic mouse model in which the KAP gene is specifically overexpressed in the cells of the renal proximal tubule, the same place where this protein is expressed endogenously, has highlighted the role of KAP in the control of metabolic syndrome and type 2 diabetes. This work has been published in the journal Scientific Reports, Nature group, and has had the collaboration of Dr. Josep Villena, head of the Laboratory of Metabolism and Obesity of the Research Unit on Diabetes and Metabolism of VHIR.
Previous studies have associated lower levels of KAP protein with diabetic nephropathy and atherosclerosis, two conditions that coexist with the metabolic syndrome. Dr. Meseguer states that “the transgenic mouse model of KAP has shown that the overexpression of KAP in the kidney protects against insulin resistance, hypertension, hepatic steatosis and inflammation of fatty tissue, induced by an obesogenic diet rich in fat”. In a cellular system, the authors of the paper also demonstrate that KAP acts by preventing the production of IL-6 by TNF, a key pathway and very relevant in the development of the syndrome. It is also shown that KAP protein is secreted in the extracellular space, attributing a hormonal effect to target tissues such as the adipose and possibly the liver.
Together with previous work from the same group, it shows that kidney-specific KAP protein plays a key role in the induction and activation of several extrarenal pathways related to cardiovascular and metabolic diseases of great impact, both on the health of citizens and on health expenditure, such as obesity and diabetes. In this sense, KAP could be a good therapeutic target to combat the metabolic syndrome.
This and other work by Dr. Meseguer’s group clearly demonstrate the role of KAP, and consequently of the kidney and androgens, in the management of cardiovascular disease and type 2 diabetes. The kidney ceases to be a passive element in the disease and becomes an active element in its control. This is an innovative and unrecognized concept that deserves to be highlighted and considered.
The metabolic syndrome:
Metabolic syndrome can be defined as a set of metabolic disorders derived, in part, from unhealthy lifestyle habits, such as sedentary lifestyles and excessive and unbalanced caloric intake. Currently, the metabolic syndrome is beginning to qualify as a global epidemic, as it affects 30% of the adult population in Western countries and 44% of US citizens over the age of 50. It has a very negative impact on the health of citizens and on the control of health expenditure.
Metabolic syndrome increases the risk of cardiovascular disease or developing type 2 diabetes. At the cellular and molecular level, this is due to effects such as chronic inflammation in adipose tissue, which is essential in the development of metabolic dysfunctions related to obesity, insulin resistance, endothelial renal dysfunction or oxidative stress, among others.
Other studies have investigated the relationship between serum concentrations of C-reactive protein cytokines (CRP), tumor necrosis factor (TNF) – α and interleukin (IL) -6, and obesity and visceral adiposity.
Overall, serum concentrations of PCR, TNF-α and IL-6 correlated significantly with weight, BMI (body mass index), waist circumference, hip circumference, and waist-to-hip ratio. In obese subjects, CRP and IL-6 correlated significantly with BMI, waist circumference and visceral fat tissue. Multiple regression analysis showed that CRP was significantly associated with BMI, while IL-6 was significantly associated with visceral adiposity in obese subjects.
Positive associations of obesity and visceral adiposity with elevated cytokine levels suggest the importance of reducing obesity and visceral adiposity to prevent elevations in cytokine levels. It has been concluded that KAP may act as a hormone-like product in extrarenal tissues by preventing events related to inflammation that are It has been concluded that KAP may act as a hormone-like product in extrarenal tissues by preventing inflammation-related events that are mediated, in part, through the IL-6 pathway and other mediators that enhance immune and inflammatory responses.