Estrogen Impairs Adipose Tissue Expansion and Cardiometabolic Profile in Obese-Diabetic Female Rats

Abstract

It has been reported that 17β-estradiol (E2) can exert beneficial effects against the development of obesity, providing women with a healthier metabolic profile and conferring cardiovascular protection. However, a growing body of evidence questions this role in the context of obesity and diabetes. We focus on the adipose tissue–heart axis to address the question of whether E2 can have metabolically detrimental effects in an obese-diabetic rat model. Female Zucker Diabetic Fatty rats were used: LEAN, fa/+; SHAM, sham-operated fa/fa; OVA, ovariectomized fa/fa, and OVA+E2, ovariectomized and E2 treated fa/fa. The secretory expression profile, tissue expansion parameters and composition of visceral adipose tissue, as well as systemic and cardiac parameters related to insulin resistance, fibrosis, and inflammation were analyzed. Ovariectomy induced an attenuation of both diabetic condition and metabolic dysfunction of adipose tissue and cardiac muscle in fa/fa rats, suggesting that E2, in the context of diabetes and obesity, loses its cardioprotective role and could even contribute to greater metabolic alterations. Adipose tissue from OVA rats showed a healthier hyperplastic expansion pattern, which could help maintain tissue function, increase adiponectin expression, and decrease pro-inflammatory adipokines. These findings should be taken into account when considering hormone replacement therapy for obese-diabetic women.

Liraglutide improves adipose tissue remodeling and mitochondrial dynamics in a visceral obesity model induced by a high-fat diet

“…To clarify this point further research is needed. Moreover, it is important to mention that in this study only male mice were studied, given that estrogens modify adipose tissue expansion as well as metabolic profile ( Martínez-Cignoni et al, 2021 ; Moreira-Pais et al, 2020 ). Furthermore, previous studies suggested that female mice would be protected against HFD-induced metabolic changes while maintaining an anti-inflammatory environment in the intra-abdominal adipose tissue ( Pettersson et al, 2012 ).…”

The G-Protein-Coupled Estrogen Receptor Agonist Prevents Cardiac Lipid Accumulation by Stimulating Cardiac Peroxisome Proliferator-Activated Receptor α: A Preclinical Study in Ovariectomized-Diabetic Rat Model

“…Some reports contradict the results of this study. For instance, Martinez-Cignoni et al ( 36 ) showed that induction of ovariectomy in diabetic animals was associated with decreased CD36 expression. The reason for these contradictory results can be due to the difference in the type of injury and duration of diabetes.…”

The evolutionary impact and influence of oestrogens on adipose tissue structure and function

“…Lastly, oestrogens also influence the capacity of the adipocyte to be filled with lipid. As will be discussed further below, oestrogens also influence the nature of fat cells themselves, making them more ‘expandable’—which refers to the ability of the fat cell to store more calories [9,16,24]. Once a cell has reached its capacity to store lipid, lipid is deposited ectopically which is associated with increased inflammation and the metabolic syndrome.…”

“…The nutritional and metabolic demands for reproduction are significantly higher in women when compared to men. SAT deposition in females provides fuel during peak times of energy requirements such as during breastfeeding, which may account for the asymmetry seen in adipose tissue deposition [24].…”