Garcinia cambogia, also known as Malabar tamarind, is native to South Asia. The crude extract of Garcinia is reported to possess anti-oxidant, anti-cancer, anti-diabetic, anti-inflammatory, hepatoprotective, anti-microbial and anti-obesity properties1. Although Garcinia possesses various biological activities, it has gained much attention due to its anti-obesity properties. This property is attributed partly to the presence of a high concentration of hydroxycitric acid (HCA).
Obesity is a chronic metabolic disorder and is associated with hypertension, hyperglycaemia and myocardial infarction. Natural supplements are on trend for weight management due to their low side effects. This article will reveal the anti-obesity mechanism associated with Garcinia (HCA).
The formation of fat from carbohydrates involves the oxidation of pyruvate to acetyl-CoA in mitochondria. ATP: citrate lyase (ACL) converts mitochondria-derived citrate into oxaloacetate and acetyl-CoA in the cytoplasm, resulting in acetyl-CoA acting as a precursor of fatty acid synthesis. It has been reported that hydroxycitric acid (HCA) inhibit ATP: citrate lyase, which leads to reduced fatty acid synthesis2. Inhibition of ACL by HCA leads to reduced acetyl-CoA and, subsequently, malonyl-CoA pool. This leads to the limited availability of two carbon groups to synthesize fats and cholesterol (Fig. 1).
Fig. 1 Anti-obesity effects of Hydroxycitric acid (Garcinia).
(Adapted from Tomar et al., 2019)
Based on the above mechanism of HCA, a clinical study on 100 obese individuals reported that HCA treatment (250 mg, BD, 3 months) reduced fat accumulation in obese individuals3.
A pre-clinical study reported that HCA treatment causes elevation of hepatic and muscle glycogen, thyroid hormone, insulin and leptin levels. Additionally, HCA promotes protein synthesis and regulates thyroid hormone levels. This might be responsible for suppressing fat accumulation4. It is reported that HCA inhibits phosphofructokinase (PFK), a crucial enzyme involved in glycolysis. This leads to a reduced glycolysis rate, leading to higher muscle glycogen content5.
To conclude, hydroxycitric acid present in Garcinia promotes weight loss by inhibiting PFK and ACL and increasing hepatic and muscle glycogen.
References:
(1) Anilkumar, A. T.; Manoharan, S.; Balasubramanian, S.; Perumal, E. Garcinia Gummi-Gutta: Phytochemicals and Pharmacological Applications. BioFactors. John Wiley and Sons Inc May 1, 2023, pp 584–599. https://doi.org/10.1002/biof.1943.
(2) Watson$ And, J. A.; Lowenstein, J. M. Citrate and the Conversion of Carbohydrate into Fat fatty acid synthesis by a combination of cytoplasm and mitochondria"; 1970; Vol. 245.
(3) Tomar, M.; Rao, R. P.; Dorairaj, P.; Koshta, A.; Suresh, S.; Rafiq, M.; Kumawat, R.; Paramesh, R.; Babu, U. V.; Venkatesh, K. V. A Clinical and Computational Study on Anti-Obesity Effects of Hydroxycitric Acid. RSC Adv 2019, 9 (32), 18578–18588. https://doi.org/10.1039/c9ra01345h.
(4) Han, N.; Li, L.; Peng, M.; Ma, H. (-)-Hydroxycitric Acid Nourishes Protein Synthesis via Altering Metabolic Directions of Amino Acids in Male Rats. Phytotherapy Research 2016, 30 (8), 1316–1329. https://doi.org/https://doi.org/10.1002/ptr.5630.
(5) McCune, S. A.; Foe, L. G.; Kemp, R. G.; Jurin, R. R. Aurintricarboxylic Acid Is a Potent Inhibitor of Phosphofructokinase. Biochemical Journal 1989, 259 (3), 925–927. https://doi.org/10.1042/bj2590925.
