Integrated analysis of proteomics‐delineated and metabolomics‐delineated hepatic metabolic responses to (−)‐hydroxycitric acid in chick embryos

Abstract

(−)‐Hydroxycitric acid [(−)‐HCA] is widely used as a nutritional supplement to control body weight and fat accumulation in animals and humans, whereas the underlying biochemical mechanism is unclear. Broiler chicken was used as a model for studies of obesity due to its natural hyperglycemia and being insulin resistant. The current study aimed to obtain a systematic view of serum metabolites and hepatic proteins and well understand the mechanism of hepatic metabolic response to (−)‐HCA treatment in chick embryos. The results showed that 22, 90, and 82 of differentially expressed proteins were identified at E14d, E19d, and H1d in chick embryos treated with (−)‐HCA, respectively. Meanwhile, 5, 83, and 88 of serum metabolites significantly changed at E14d, E19d, and H1d in chick embryos after (−)‐HCA treatment. Bioinformatics analysis showed that the key proteins and metabolites, which were significantly altered in chick embryos treated with (−)‐HCA, were mainly involved in the citrate cycle, glycolysis/gluconeogenesis, fatty acid metabolism, and pyruvate metabolism. Our data indicated that (−)‐HCA treatment might promote fat metabolism via regulating the key protein expression levels and metabolite contents in the citrate cycle, glycolysis/gluconeogenesis, and oxidative phosphorylation during chicken embryonic development. These results will deepen our understanding of the mechanism of fat reduction by (−)‐HCA and provide substantial information for (−)‐HCA as a nutritional supplement to control body weight gain and curb obesity‐related diseases.

Potential role of ALDH3A2 on the lipid and glucose metabolism regulated by (‐)‐hydroxycitric acid in chicken embryos

“…Recently, our laboratory found that (-)-HCA treatment significantly increased the aldehyde dehydrogenase 3 family member A2 (ALDH3A2) expression in chicken embryos (Peng, He, Li, Li, & Ma, 2018). ALDH3A2 is a classical target gene of peroxisome proliferatoractivated receptor α (PPARα); and PPARα plays a key role in regulation of cellular lipid and energy metabolism (Vega, Huss, & Kelly, 2000).…”

(−)-Hydroxycitric Acid Influenced Fat Metabolism via Modulating of Glucose-6-phosphate Isomerase Expression in Chicken Embryos

“…Importantly, our recently surprising discovery was that GPI protein level was markedly enhanced in chicken embryos after treatment with (−)-HCA. 21 GPI is an essential enzyme in glycolytic and gluconeogenic processes that catalyzes reversible isomerization. 22 This study indicated that in chicken embryos, pretransfection with sh2-GPI had reversed the suppressing effect of (−)-HCA on lipid droplet and triglyceride contents.…”

“…It has been widely proved that glucose metabolism is closely related to lipid metabolism in the body, and acetyl-CoA is a key factor in the transformation of glycolipid metabolites. Importantly, our recently surprising discovery was that GPI protein level was markedly enhanced in chicken embryos after treatment with (−)-HCA . GPI is an essential enzyme in glycolytic and gluconeogenic processes that catalyzes reversible isomerization .…”

“…As an ATP-citrate lyase competitive inhibitor, (−)-HCA reduced the acetyl-CoA content and then regulated the metabolism of glucose and lipid . Our laboratory surprisingly discovered that (−)-HCA significantly increased the protein expression level of GPI (glucose-6-phosphote isomerase) in chicken embryos, which also mainly enriched the glucose metabolic pathway . GPI plays an important role in gluconeogenesis and glycolysis, it catalyzed the interconversion of fructose-6-phosphate and glucose-6-phosphate .…”

“…7 Our laboratory surprisingly discovered that (−)-HCA significantly increased the protein expression level of GPI (glucose-6phosphote isomerase) in chicken embryos, which also mainly enriched the glucose metabolic pathway. 21 GPI plays an important role in gluconeogenesis and glycolysis, it catalyzed the interconversion of fructose-6-phosphate and glucose-6phosphate. 22 GPI also can guide the glucose flow into the pentose phosphate pathway to produce NADPH, which is necessary for lipid metabolism.…”