Curcumin improves metabolic response and increases expression of thermogenesis-associated markers in adipose tissue of male offspring from obese dams

Obesity is one of the most serious public health problems worldwide, especially because of its increasing prevalence, high impact on healthcare costs, and its close relationship to several chronic diseases, including cardiovascular diseases, diabetes, non-alcoholic fatty liver disease, and some types of cancer (Williams et al., 2015; Kelly et al., 2008; Withrow and Alter, 2011). It is characterized by the excessive accumulation of body fat, usually identified by a Body Mass Index (BMI) ≥ 30 kg/m2, and is a multifactorial metabolic disorder that involves genetic, epigenetic, social, economic, and environmental factors (such as a sedentary lifestyle and the consumption of high-calorie diets) (Gonzalez-Muniesa et al., 2017; Heymsfield and Wadden, 2017; Chait and den Hartigh, 2020).

It is known that being overweight during pregnancy and/or pre-pregnancy can contribute to unfavorable maternal-fetal outcomes, and women with obesity are at increased risk for the development of pregnancy-related complications, such as gestational diabetes, hypertensive syndromes, fetal macrosomia and/or distress, prolonged labor, surgical delivery, intrauterine growth restriction, cephalopelvic disproportion, perinatal death, and prematurity (Aune et al., 2014; Gaillard et al., 2013; Cnattingius et al., 2013; Ruager-Martin et al., 2010; Godfrey et al., 2017).

In addition to the maternal-fetal complications associated with obesity, it is also recognized that maternal overweight has long-term adverse health outcomes for offspring in adulthood (Godfrey et al., 2017). Studies indicate that maternal obesity increases the risk of the offspring developing obesity and altering body composition in childhood and adulthood and, in addition, also has an impact on cardiometabolic health with dysregulation of glycemic and lipid metabolism, besides predisposing to the occurrence of hypertension and vascular dysfunction (Eriksson et al., 2015; Chandrasekaran and Neal-Perry, 2017; Contu and Hawkes, 2017; Shrestha et al., 2020; Glastras et al., 2018). Nonetheless, the pathophysiological mechanisms that correlate maternal obesity to outcomes in the offspring still lack further understanding.

Adipose tissue is the main site involved in the pathophysiological mechanisms of obesity (McGown et al., 2014; Cypess, 2022). According to embryonic, morphological, and functional characteristics, it is divided into at least two subtypes: white adipose tissue (WAT) and brown adipose tissue (BAT) (Chait and den Hartigh, 2020; Villarroya et al., 2017). The BAT is rich in mitochondria, has dense vasculature and (adrenergic) innervation, and has its cytoplasm filled with small multilocular fat droplets (Gavalda-Navarro et al., 2022). Brown adipocytes have a high concentration of the uncoupling protein (UCP1) in the inner membrane of the mitochondria, which are responsible for performing non-shivering thermogenesis in mammals, an important mechanism for heat production and energy expenditure (Villarroya et al., 2019).

Furthermore, it was recently identified that subpopulations of the WAT can differentiate into beige (browning) adipocytes, which express, although reversibly, and depending on the environmental stimulus, markers related to the thermogenesis process (Vargas-Castillo et al., 2021). In the context of maternal obesity and its effects on offspring, little is known about the role of adipose tissue, especially brown and inguinal white (iWAT).

Curcumin (1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione) is the main natural polyphenol found in the rhizome of Curcuma longa (turmeric) and other types of Curcuma spp. (Pulido-Moran et al., 2016). Studies have shown that curcumin can be targeted by several signaling molecules, in addition to demonstrating activity at the cellular level, thus regulating important metabolic pathways. In addition, it appears to exert beneficial effects on inflammatory and metabolic conditions (Hewlings and Kalman, 2017; Vera-Ramirez et al., 2013; Aggarwal, 2010; Ejaz et al., 2009; Shao et al., 2012; Yang et al., 2014). While there appear to be numerous therapeutic benefits to curcumin supplementation, little is known about its effects on adipose tissue.

Given this promising context, this study evaluated the effects of maternal supplementation with curcumin during the pregnancy-lactation period on the anthrpometric and metabolic parameters, as well as the expression of thermogenesis-associated markers in the adipose tissue of offspring fed a hyperglycemic diet.

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