Inhibition of pyruvate dehydrogenase kinase-4 by l-glutamine protects pregnant rats against fructose-induced obesity and hepatic lipid accumulation

Oral L-glutamine rescues fructose-induced poor fetal outcome by preventing placental triglyceride and uric acid accumulation in Wistar rats

“…Glutamine supplementation attenuated excess lipid in the placentae of pregnant rats that consumed high fructose-enriched drink High fructose consumption during pregnancy led to excess lipid in the placenta with correspondent increase in triglyceride (Figure 4a), total cholesterol (Figure 4b), low density lipoprotein-cholesterol (Figure 4c) and atherogenic lipid (Figure 4d & e) without alteration in free fatty acid (Figure 4f) when compared with control group, suggesting that maternal high fructose consumption increased placental lipid influx as a result of increased lipolysis that is associated with insulin resistance [15]. Accumulation of excess lipid in non-adipose cells results in oxidative stress and/or lipotoxicity [17,20]. However, these alterations were attenuated when fructose consumption was supplemented with GLN (Figure 4a, b, c, d &e).…”

“…Excessive fructose consumption through high fructose corn syrup (HFCS) and as added sugar in soft drinks is globally on the rise despite its implication in the development of metabolic syndrome. In addition, several studies, including earlier studies from our laboratory animals have demonstrated that high fructose consumption even in pregnancy leads to IR and hyperuricemia [15,16,17], which are the strong predictors of metabolic syndrome and T2D [18]. In fact, indiscriminate fructose consumption during pregnancy has been reported to disrupt maternal metabolic homeostasis, thereby defecting placental function and fetal development [19], potentially increasing the offspring's risk for metabolic health mayhem later in life [19,20].…”

“…Standardized colorimetric methods using reagents obtained from Randox Laboratory Ltd. (Co. Antrim, UK) was used to determine the concentration of triglycerides (TG), total cholesterol (TC), high density lipoprotein-cholesterol (HDLc), low density lipoprotein-cholesterol (LDLc) and free fatty acid (FFA) However, the quantification of the tissue concentration of TG, TC, HDLc, LDLc and FFA (non-esterified) were determined by coupled enzyme assays which result in colorimetric (570 nm) products proportional to the TG, TC, HDLc, LDLc and FFA present respectively. Ratios of TG/HDLc and TC/HDLc were determined as atherogenic lipids [17,38].…”

“…Adenosine monophosphate deaminase converts AMP to xanthine, which is then converted to uric acid by xanthine oxidase, uric acid extracellularly acts as a potent antioxidant and in excess intracellularly triggers oxidative stress, causing cellular dysfunction [18,19]. Similarly, excess uric acid can also provoke de novo lipogenesis thereby causing lipotoxicity with consequent promotion of oxidative stress and inflammatory response, which are features of IR-related disorders such as obesity, T2D, non-alcoholic fatty liver disease among others [15,17,20].…”

“…It mediates insulin secretion, and acts as an alternative substrate for energy regulation in fasting tissue or T2D [27,28]. Several studies in animals and humans have reported the benefits of GLN in metabolic disorders [17,29,30,31,32]. Interestingly, GLN is a modulator of cytoprotective proteins that are beneficial in oxidative insult [26], and it contributes majorly to the endogenous synthesis of glutathione (GSH) [28].…”