Dietary glycotoxins affect scavenger receptor expression and the hormonal profile of female rats

Abstract

The levels of advanced glycation end products (AGEs) are increased under conditions of impaired glucose metabolism and/or oxidative stress, promoting insulin resistance and other endocrine abnormalities. AGEs play a major role in the pathogenesis of several diseases such as diabetes, atherosclerosis, polycystic ovary syndrome and Alzheimer's disease, contributing to progressive ageing. Receptor-based clearance of AGEs by the receptor for AGE (RAGE) and/or the macrophage scavenger receptor A (SR-A) is considered as a main factor for the regulation of the concentration of AGEs under these conditions. This study aimed to investigate the expression of RAGE (AGER) and SR-A (MSR1) under high/low-dietary AGE conditions in vivo and their potential contribution to the metabolic and sex hormonal profile of female rats. Female Wistar rats were fed a low-AGE or high-AGE diet for 3 months. Serum samples were collected at baseline and at the completion of the 3-month period for the measurements of metabolic and hormonal parameters. Peripheral blood mononuclear cells (PBMCs) were isolated for the determination of the expression of RAGE and SR-A. The high-AGE diet-fed rats exhibited increased glucose, insulin and testosterone levels as well as decreased oestradiol and progesterone levels compared with the low-AGE diet-fed ones, thus indicating a metabolic and hormonal dysregulation attributed to high-AGE dietary exposure. The expression of RAGE was significantly down-regulated in the PBMCs of the high-AGE diet-fed rats (PZ0.041), and it was correlated negatively with insulin and testosterone levels and positively with progesterone levels. The expression of SR-A was also decreased in the high-AGE diet-fed rats to marginal significance. Decreased monocytic expression of scavenger receptors such as RAGE and SR-A may result in a higher deposition of AGEs in peripheral endocrine tissues, thus promoting endocrine-related abnormalities and diseases.

Advanced Glycation End Products (AGEs) May Be a Striking Link Between Modern Diet and Health

“…A study on Wistar rats having highly expressed RAGE in mononuclear cells (peripheral blood) revealed low levels of the hormones, along with high levels of glucose, insulin, and testosterone. This data verified that PCOS is an endocrine disorder that is highly influenced by metabolism and diet [71,92,108]. Increased levels of anti-Mullerian hormones (AMH) have a sustainable effect on the reproductive system by provoking anovulation via direct inhibition of FSH.…”

Dietary Advanced Glycation End Products Have Sex- and Age-Dependent Effects on Vertebral Bone Microstructure and Mechanical Function in Mice

“…(59,60) Sex hormones may play a role on the AGE-mediated changes in vertebral structure and function observed in this study. Chatzigeorgiou and colleagues (61) found that a high-AGE diet increased serum glucose, insulin, and testosterone levels, as well as decreased estradiol and progesterone levels, suggesting there may exist a metabolic and hormonal dysregulation attributed to high-AGE dietary ingestion. Consequently, this study highlights a need for future investigations to identify sex-dependent tissue and cellular mechanisms for these observed effects and means of intervention.…”

A prospective study of soluble receptor for advanced glycation end-products and colorectal cancer risk in postmenopausal women

“…However, we did not observe a significant interaction between CML-AGE and BMI on CRC risk in our study. Because levels of CML-AGE have also been shown to be modulated by its receptors, including galectin 3, macrophage scavenger receptor [57], AGER-1 and sirtuin 1 [58], its full impact at the tissue level may need to be considered in the context of its receptors.…”