(-)-Hydroxycitric Acid Reduced Lipid Droplets Accumulation Via Decreasing Acetyl-Coa Supply and Accelerating Energy Metabolism in Cultured Primary Chicken Hepatocytes

Abstract

Background/Aims: (-)-Hydroxycitric acid (HCA) had been shown to suppress fat accumulation in animals and humans, while the underlying biochemical mechanism is not fully understood, especially little information is available on whether (-)-HCA regulates energy metabolism and consequently affects fat deposition. Methods: Hepatocytes were cultured for 24 h and then exposed to (-)-HCA (0, 1, 10, 50 µM), enzyme protein content was determined by ELISA; lipid metabolism gene mRNA levels were detected by RT-PCR. Results: (-)-HCA significantly decreased the number and total area of lipid droplets. ATP-citrate lyase, fatty acid synthase and sterol regulatory element binding protein-1c mRNA level were significantly decreased after (-)-HCA treatment, whereas peroxisome proliferator-activated receptor α mRNA level was significantly increased. (-)-HCA significantly decreased ATP-citrate lyase activity and acetyl-CoA content in cytosol, but significantly increased glucose consumption and mitochondrial oxygen consumption rate. (-)-HCA promoted the activity/content of glucokinase, phosphofructokinase-1, pyruvate kinase, pyruvate dehydrogenase, citrate synthase, aconitase, succinate dehydrogenase, malate dehydrogenase, NADH dehydrogenase and ATP synthase remarkably. Conclusions: (-)-HCA decreased lipid droplets accumulation by reducing acetyl-CoA supply, which mainly achieved via inhibition of ATP-citrate lyase, and accelerating energy metabolism in chicken hepatocytes. These results proposed a biochemical mechanism of fat reduction by (-)-HCA in broiler chickens in term of energy metabolism.

The methanolic extract of Garcinia atroviridis (MeGa) reduces body weight and food intake, and improves lipid profiles by altering the lipid metabolism: a rat model

“…However, (-)-HCAtreated broiler chicken and primary culture of chicken hepatocytes have been reported to show changes in the hepatic mRNA expressions involved in the metabolism of lipids. Expression of genes related to the synthesis of fatty acids such as FAS, sterol regulatory element binding protein-1c (SREBP-1c)], and ACLY genes were downregulated, while the peroxisome proliferators-activated receptor α (PPARα) gene was upregulated (Han et al, 2016b;Li et al, 2017). Further metabolomics investigation indicated that (-)-HCA was involved in the metabolisms of amino acids, protein synthesis, citric acid cycle, and synthesis of uric acid and fatty acids in controlling weight gain and lipid accumulation (Peng et al, 2017).…”

Therapeutic Effect of Garcinia cambogia Extract and Hydroxycitric Acid Inhibiting Hypoxia-Inducible Factor in a Murine Model of Age-Related Macular Degeneration

“…Therefore, a preventive effect against hyperphagia is also expected [31,32,33]. In chicken hepatocytes, HCA decreased the accumulation of lipid droplets and accelerated energy metabolism [34]. HCA protected the cells from ER stress by increasing the antioxidant status and mitochondrial functions [35].…”

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

“…(‐)‐Hydroxycitric acid ((‐)‐HCA), extracted from the dried fruit rind of Garcinia cambogia , has demonstrated to reduce body weight gain (Fassina et al, ), inhibit de novo fatty acid synthesis (Chuah, Ho, Beh, & Yeap, ), increase fat oxidation (Amin, Kamel, & Abd Eltawab, ), promote protein synthesis (Han, Li, Peng, & Ma, ), and enhance energy expenditure in animals and humans (Ishihara, Oyaizu, Onuki, Lim, & Fushiki, ; Kim et al, ). In avian, supplemental with (‐)‐HCA inhibited fatty acid synthesis by reducing the acetyl‐CoA supply via promotion of the citric acid cycle in primary chicken hepatocytes (Li, Peng, Ge, Yu, & Ma, ) or in broiler chickens (Peng, Han, Li, & Ma, ). Previous study showed that (‐)‐HCA, as a potent competitive inhibitor of ATP‐citrate lyase (Sullivan, Hamilton, Miller, & Wheatley, ), blocked the citrate cleavage into oxaloacetate and acetyl‐CoA which eventually limits the availability of acetyl‐CoA units required for fatty acid synthesis in animals and humans (Ishihara et al, ).…”