Relationship between Garcinia cambogia-Induced Impairment of Spermatogenesis and Meiosis-Activating Sterol Production in Rat Testis

Abstract

Summary Dietary supplements for body fat reduction have become popular, particularly in developed countries. Garcinia cambogia (GA) is one such supplement, and its active component is (−)-hydroxycitric acid ((−)-HCA), a competitive inhibitor of ATP citrate lyase, which is responsible for producing acetyl CoA from citric acid. Recently we have found that administration of (−)-HCA-containing GA markedly reduces testis weight in male Zucker obese rats. In particular, histopathological examinations revealed testicular atrophy and impairment of spermatogenesis. In the present study, we investigated the cause of the impaired spermatogenesis after ingestion of GA containing (−)-HCA at 102 mmol / kg diet in young Fischer 344 male rats. Among hormones related to spermatogenesis, the serum level of inhibin-B was significantly lower and that of follicle-stimulating hormone (FSH) was higher in the GA group. The level of testis meiosis-activating sterol (T-MAS), which is an intermediate in cholesterol biosynthesis from acetyl CoA and is presumed to transmit a signal for spermatogenesis, was statistically lower in the testes of rats administered GA. We hypothesize from these results that (−)-HCA-mediated inhibition of ATP citrate lyase in rats fed GA leads to diminished accumulation of MAS substances, thus resulting in impairment of spermatogenesis.

Effect of Garcinia cambogia Administration on Female Reproductive Organs in Rats

“…We have reported recently that the high dose of (−)-HCAcontaining GA ((−)-HCA levels; 102 mmol / kg diet or higher) causes potent testicular atrophy and toxicity in male rats [7], and suggested that (−)-HCA-mediated inhibition of ATP citrate lyase leads to diminished accumulation of T-MAS in rat testis [8], thus probably resulting in impairment of spermatogenesis. In the present study, we examined the effect of GA administration on safety with special reference to female reproductive organs in rats.…”

“…In the former study, we focused the effect of GA administration on body fat accumulation using Zucker obese rats [7], and in the previous study, we examined the effect of GA administration on testicular toxicity in Fischer 344 (F344) strain rats [8]. Since the aim of the current study was to elucidate safety in female rats, we used rats of SD-IGS strain, a strain often used lately in toxicological study together with F344 strain, and a diet containing (−)-HCA at 154mmol /kg diet, the highest dose in the former study [7].…”

“…From the results obtained in male rat testis [7,8], we hypothesized that the accumulation of MAS substances in rat ovary might be affected by the competitive inhibition of ATP citrate lyase by (−)-HCA. So, we measured the concentrations of FF-MAS, T-MAS and cholesterol in rat ovary (Fig.…”

“…To consider the safety of GA administration in female rats, compared with that in male rats in our previous studies [7,8], we performed histopathological examination of the ovaries (Table 3). After two weeks of GA feeding, there were no evident morphological abnormalities in the follicle and corpus luteum.…”

“…So, 51 mmol / kg diet was deemed to be the no observed adverse effect level (NOAEL) in these rats. Moreover, we suggested that (−)-HCA-mediated inhibition of ATP citrate lyase in rats fed GA leads to diminished accumulation of T-MAS in rat testis, resulting in impairment of spermatogenesis [8]. Hence, care should be taken with GA intake in males.…”