title: Body weight and abdominal fat gene expression profile in response to a novel hydroxycitric acid-based dietary supplement.
abstract: Obesity is a global public health problem, with about 315 million people worldwide estimated to fall into the WHO-defined obesity categories. Traditional herbal medicines may have some potential in managing obesity. Botanical dietary supplements often contain complex mixtures of phytochemicals that have additive or synergistic interactions. The dried fruit rind of Garcinia cambogia, also known as Malabar tamarind, is a unique source of (-)-hydroxycitric acid (HCA), which exhibits a distinct sour taste and has been safely used for centuries in Southeastern Asia to make meals more filling. Recently it has been demonstrated that HCA-SX or Super Citrimax, a novel derivative of HCA, is safe when taken orally and that HCA-SX is bioavailable in the human plasma as studied by GC-MS. Although HCA-SX has been observed to be conditionally effective in weight management in experimental animals as well as in humans, its mechanism of action remains to be understood. We sought to determine the effects of low-dose oral HCA-SX on the body weight and abdominal fat gene expression profile of Sprague-Dawley rats. We observed that at doses relevant for human consumption dietary HCA-SX significantly contained body weight growth. This response was associated with lowered abdominal fat leptin expression while plasma leptin levels remained unaffected. Repeated high-density microarray analysis of 9960 genes and ESTs present in the fat tissue identified a small set (approximately 1% of all genes screened) of specific genes sensitive to dietary HCA-SX. Other genes, including vital genes transcribing for mitochondrial/nuclear proteins and which are necessary for fundamental support of the tissue, were not affected by HCA-SX. Under the current experimental conditions, HCA-SX proved to be effective in restricting body weight gain in adult rats. Functional characterization of HCA-SX-sensitive genes revealed that upregulation of genes encoding serotonin receptors represent a distinct effect of dietary HCA-SX supplementation.
authors.affiliation: Laboratory of Molecular Medicine, Department of Surgery, The Ohio State University Medical Center, Columbus, OH 43210, USA.
authors.forename: Sashwati
authors.initials: S
authors.lastname: Roy
authors.forename: Cameron
authors.initials: C
authors.lastname: Rink
authors.forename: Savita
authors.initials: S
authors.lastname: Khanna
authors.forename: Christina
authors.initials: C
authors.lastname: Phillips
authors.forename: Debasis
authors.initials: D
authors.lastname: Bagchi
authors.forename: Manashi
authors.initials: M
authors.lastname: Bagchi
authors.forename: Chandan K
authors.initials: CK
authors.lastname: Sen
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D019440:Anti-Obesity Agents / Q000494:pharmacology; D001835:Body Weight / Q000187:drug effects*; D002951:Citrates / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D019587:Dietary Supplements; D015536:Down-Regulation; D029761:Garcinia cambogia / Q000737:chemistry; D015870:Gene Expression / Q000187:drug effects*; D020869:Gene Expression Profiling; D051272:Glucose Transporter Type 1; D051275:Glucose Transporter Type 4; D020738:Leptin / Q000097:blood / Q000235:genetics; D024101:Mitochondrial Proteins / Q000235:genetics; D009004:Monosaccharide Transport Proteins / Q000235:genetics; D009124:Muscle Proteins / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics; D009765:Obesity / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D028321:Plant Preparations / Q000737:chemistry / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D011956:Receptors, Cell Surface / Q000235:genetics; D015854:Up-Regulation
chemical_list: D019440:Anti-Obesity Agents; D002951:Citrates; D051272:Glucose Transporter Type 1; D051275:Glucose Transporter Type 4; D020738:Leptin; D024101:Mitochondrial Proteins; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; D009687:Nuclear Proteins; D028321:Plant Preparations; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; C495694:Slc2a4 protein, rat; C495383:Super Citrimax; C007999:hydroxycitric acid