Garcinia cambogia water extract alleviates insulin resistance and hepatic lipid accumulation in mice fed a high-fat diet

Background Garcinia cambogia is widely used as a weight-loss supplement, and it is reported to be negatively associated with metabolic diseases including insulin resistance (IR), type 2 diabetes mellitus (T2DM), non-alcoholic fatty liver disease (NAFLD), and dyslipidemia. Objective This study aimed to investigate the effect of G. cambogia water extract (GE) on high-fat diet (HFD)-induced obesity, IR, and hepatic lipid accumulation. Design C57BL/6 male mice were fed HFD with or without GE, GED and GEP for 16 weeks, and the mice were subjected to insulin tolerance tests and liver histological analysis. The hydroxycitric acid (HCA) levels of GE, GED, and GEP were measured by high-performance liquid chromatography. Results The results showed that GE significantly reduced HFD-induced body weight gain (P < 0.001), alleviated IR (P < 0.01), reduced serum total cholesterol (TC) (P < 0.001), and attenuated HFD-induced hepatic lipid accumulation. To investigate the constituent that was responsible for these effects, we separated GE into the component that dissolved in ethanol (GED) and the component that was precipitated by ethanol (GEP). Further mouse experiments showed that both GED and GEP were effective, but GED (which was used at a dose of 4 g/L) was more effective than GEP (which was used at a lower dose of 1 g/L). The HCA levels in GED and GEP were similar, although less than in GE. HCA may be the effective component in GE. Conclusion This study provides evidence that G. cambogia can be used as a natural supplement to alleviate IR and hepatic lipid accumulation.

[1]  Aditi Roy,et al.  A Multidisciplinary Approach and Current Perspective of Nonalcoholic Fatty Liver Disease: A Systematic Review , 2022, Cureus.

[2]  Raghvendra Mall,et al.  Dysregulated Metabolic Pathways in Subjects with Obesity and Metabolic Syndrome , 2022, International journal of molecular sciences.

[3]  R. Lesmana,et al.  Potential roles of Garcinia family as antimetabolic syndrome , 2022, Journal of advanced pharmaceutical technology & research.

[4]  Jiezhun Gu,et al.  Garcinia Cambogia, Either Alone or in Combination with Green Tea Causes Moderate to Severe Liver Injury. , 2021, Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association.

[5]  Seon-Bong Kim,et al.  Arousal-Inducing Effect of Garcinia cambogia Peel Extract in Pentobarbital-Induced Sleep Test and Electroencephalographic Analysis , 2021, Nutrients.

[6]  C. Myung,et al.  Garcinia cambogia Ameliorates Non-Alcoholic Fatty Liver Disease by Inhibiting Oxidative Stress-Mediated Steatosis and Apoptosis through NRF2-ARE Activation , 2021, Antioxidants.

[7]  C. Myung,et al.  Garcinia cambogia attenuates adipogenesis by affecting CEBPB and SQSTM1/p62-mediated selective autophagic degradation of KLF3 through RPS6KA1 and STAT3 suppression , 2021, Autophagy.

[8]  Y. Ye,et al.  Polyisoprenylated benzophenone derivatives from Garcinia cambogia and their anti-inflammatory activities. , 2021, Food & function.

[9]  J. Pedro-Botet,et al.  Recognizing obesity as a disease: A true challenge , 2021, Revista Clínica Española (English Edition).

[10]  Qiqi Zhu,et al.  5-Bis-(2,6-difluoro-benzylidene) Cyclopentanone Acts as a Selective 11β-Hydroxysteroid Dehydrogenase one Inhibitor to Treat Diet-Induced Nonalcoholic Fatty Liver Disease in Mice , 2021, Frontiers in Pharmacology.

[11]  J. Sowers,et al.  Insulin resistance, cardiovascular stiffening and cardiovascular disease. , 2021, Metabolism: clinical and experimental.

[12]  N. Tennagels,et al.  Insulin Fused to Apolipoprotein A-I Reduces Body Weight and Steatosis in DB/DB Mice , 2021, Frontiers in Pharmacology.

[13]  Jiali Yang,et al.  4-Hydroxyisoleucine Alleviates Macrophage-Related Chronic Inflammation and Metabolic Syndrome in Mice Fed a High-Fat Diet , 2021, Frontiers in Pharmacology.

[14]  C. Myung,et al.  Garcinia cambogia suppresses adipogenesis in 3T3‐L1 cells by inhibiting p90RSK and Stat3 activation during mitotic clonal expansion , 2020, Journal of cellular physiology.

[15]  N. Kawada,et al.  The Role of Insulin Resistance and Diabetes in Nonalcoholic Fatty Liver Disease , 2020, International journal of molecular sciences.

[16]  J. Tur,et al.  Dietary fat intake and metabolic syndrome in adults: A systematic review. , 2019, Nutrition, metabolism, and cardiovascular diseases : NMCD.

[17]  Haitian Ma,et al.  (-)-Hydroxycitric Acid Suppresses Lipid Droplet Accumulation and Accelerates Energy Metabolism via Activation of the Adiponectin-AMPK Signaling Pathway in Broiler Chickens. , 2019, Journal of agricultural and food chemistry.

[18]  S. Akira,et al.  Caffeine-stimulated muscle IL-6 mediates alleviation of non-alcoholic fatty liver disease. , 2019, Biochimica et biophysica acta. Molecular and cell biology of lipids.

[19]  Y. Abdel-Mottaleb,et al.  Raspberry ketone and Garcinia Cambogia rebalanced disrupted insulin resistance and leptin signaling in rats fed high fat fructose diet. , 2019, Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie.

[20]  Young‐Mi Lee,et al.  Chrysanthemum indicum L. ethanol extract reduces high-fat diet-induced obesity in mice. , 2018, Experimental and therapeutic medicine.

[21]  M. S. Poblador,et al.  Long-term effects of Garcinia cambogia/Glucomannan on weight loss in people with obesity, PLIN4, FTO and Trp64Arg polymorphisms , 2018, BMC Complementary and Alternative Medicine.

[22]  B. Zarić,et al.  Link between Metabolic Syndrome and Insulin Resistance. , 2016, Current vascular pharmacology.

[23]  Haitian Ma,et al.  (‐)‐Hydroxycitric Acid Nourishes Protein Synthesis via Altering Metabolic Directions of Amino Acids in Male Rats , 2016, Phytotherapy research : PTR.

[24]  A. Zagayko,et al.  The impact of hydroxycitric acid on the lipid metabolism profile under experimental insulin resistance syndrome of Syrian hamsters. , 2016, Ukrainian biochemical journal.

[25]  M. Sridhar,et al.  Antihyperlipidemic and antioxidant activities of the ethanolic extract of Garcinia cambogia on high fat diet-fed rats , 2016, Journal of complementary & integrative medicine.

[26]  Patrícia Fassina,et al.  THE EFFECT OF GARCINIA CAMBOGIA AS COADJUVANT IN THE WEIGHT LOSS PROCESS. , 2015, Nutricion hospitalaria.

[27]  G. Poropat,et al.  Nonalcoholic steatohepatitis: emerging targeted therapies to optimize treatment options , 2015, Drug design, development and therapy.

[28]  I. Vermaak,et al.  A comprehensive scientific overview of Garcinia cambogia. , 2015, Fitoterapia.

[29]  R. Sripradha,et al.  Efficacy of garcinia cambogia on body weight, inflammation and glucose tolerance in high fat fed male wistar rats. , 2015, Journal of clinical and diagnostic research : JCDR.

[30]  M. Rau,et al.  Non-alcoholic fatty liver disease: epidemiology, clinical course, investigation, and treatment. , 2014, Deutsches Arzteblatt international.

[31]  C. Vasques,et al.  Hypolipemic Effect of Garcinia cambogia in Obese Women , 2014, Phytotherapy research : PTR.

[32]  Ioannis Kyrou,et al.  Clinical Problems Caused by Obesity , 2014 .

[33]  H. Preuss,et al.  Hydroxycitric acid does not promote inflammation or liver toxicity. , 2013, World journal of gastroenterology.

[34]  Mi-Kyung Lee,et al.  Garcinia Cambogia attenuates diet-induced adiposity but exacerbates hepatic collagen accumulation and inflammation. , 2013, World journal of gastroenterology.

[35]  S. Yeap,et al.  Updates on Antiobesity Effect of Garcinia Origin (−)-HCA , 2013, Evidence-based complementary and alternative medicine : eCAM.

[36]  T. Bilal,et al.  Effect of Garcinia cambogia extract on body weight gain, feed intake and feed conversion ratio, and serum non-esterified fatty acids and C-reactive protein levels in rats fed with atherogenic diet , 2012 .

[37]  J. Salas-Salvadó,et al.  Evaluation of the Safety and Efficacy of Hydroxycitric Acid or Garcinia cambogia Extracts in Humans , 2012, Critical reviews in food science and nutrition.

[38]  K. Amin,et al.  The relation of high fat diet, metabolic disturbances and brain oxidative dysfunction: modulation by hydroxy citric acid , 2011, Lipids in Health and Disease.

[39]  E. Ernst,et al.  The Use of Garcinia Extract (Hydroxycitric Acid) as a Weight loss Supplement: A Systematic Review and Meta-Analysis of Randomised Clinical Trials , 2010, Journal of obesity.

[40]  J. Yun Possible anti-obesity therapeutics from nature--a review. , 2010, Phytochemistry.

[41]  T. Park,et al.  Garcinia cambogia Extract Ameliorates Visceral Adiposity in C57BL/6J Mice Fed on a High-Fat Diet , 2008, Bioscience, biotechnology, and biochemistry.

[42]  D. Bagchi,et al.  Bioefficacy of a novel calcium-potassium salt of (-)-hydroxycitric acid. , 2005, Mutation research.

[43]  G. Yoshino,et al.  Effects of garcinia cambogia (Hydroxycitric Acid) on visceral fat accumulation: a double-blind, randomized, placebo-controlled trial. , 2003, Current therapeutic research, clinical and experimental.

[44]  M. Furuse,et al.  Effect of Garcinia cambogia extract on serum leptin and insulin in mice. , 2003, Fitoterapia.

[45]  N. Bergeron,et al.  Gas chromatography/mass spectrometry method to quantify blood hydroxycitrate concentration. , 2001, Analytical biochemistry.

[46]  J. G. Hamilton,et al.  Effect of (−)-hydroxycitrate upon the accumulation of lipid in the rat: II. Appetite , 1974, Lipids.

[47]  J. G. Hamilton,et al.  Effect of (−)-hydroxycitrate upon the accumulation of lipid in the rat: I. Lipogenesis , 1974, Lipids.

[48]  Y. S. Lewis,et al.  (−)-Hydroxycitric acid—the principal acid in the fruits of Garcinia cambogia desr. , 1965 .

[49]  A. Engin,et al.  The Definition and Prevalence of Obesity and Metabolic Syndrome. , 2017, Advances in experimental medicine and biology.

[50]  European Association for the Study of the Liver,et al.  EASL-EASD-EASO Clinical Practice Guidelines for the Management of Non-Alcoholic Fatty Liver Disease , 2016, Obesity Facts.

[51]  André Tchernof,et al.  Pathophysiology of human visceral obesity: an update. , 2013, Physiological reviews.