Association between Equol Production Status and Nonalcoholic Steatohepatitis.

Takemi Akahane,Yasuhiko Sawada,Hitoshi Yoshiji,Yuki Tsuji,Koh Kitagawa,Masanori Furukawa,Kosuke Kaji,Daisuke Kaya,Yukihisa Fujinaga,Hideto Kawaratani,Haruna Miyakawa,Hiroaki Takaya,Kei Moriya,Ryuichi Noguchi,Tadashi Namisaki,Takahiro Ozutsumi

doi:10.3390/ijms222111904

Takemi Akahane, Yasuhiko Sawada + Show 14 more

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https://doi.org/10.3390/ijms222111904

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Abstract

Equol is a metabolite of daidzein, a major soybean isoflavone with estrogenic and antioxidant activities. As the production of equol depends on the presence of certain members of the intestinal microflora, not all individuals can produce equol. We examined the relationship between NASH histological features and equol production. In an animal model, obese OLETF rats were intraperitoneally injected with a porcine serum to augment liver fibrogenesis. Equol-rich soy product, SE5-OH was orally administered during the experimental period. Treatment with SE5-OH markedly attenuated the development of liver fibrosis and expression of alpha-smooth muscle actin. In clinical research, 38 NAFLD patients (13 men and 25 women) were included. The degree of fibrosis and ballooning in equol-nonproducers was significantly higher than in equol-producers in women. The percentage of nonproducers with NAFLD activity score (NAS) ≥ 5 was significantly higher than that of producers. None of the histological features were significantly different between nonproducers and producers in men. Decision tree analysis identified predictors for NAS ≥ 5 in women. The status of equol production was the strongest predictor, followed by fasting glucose. Since equol can be noninvasively detected in urine, it can be applied as a screening tool for the progression of NASH in women.

Highlights

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease globally, representing a significant health burden worldwide
We showed that treatment with SE5-OH markedly attenuated the development of liver fibrosis and the expression of alpha-smooth muscle actin in male Otsuka Long-Evans Tokushima fatty (OLETF) rats, and in the clinical study, the degree of fibrosis and ballooning in equol nonproducers was significantly higher than that of producers in women with nonalcoholic steatohepatitis (NASH)
As most women in this study were menopausal and the menstruation of nonproducers who had not reached menopause was irregular or amenorrheic, it could be suggested that the status of equol production is associated with the pathogenesis of NASH in menopausal women or women with low estrogen secretion

Summary

Introduction

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease globally, representing a significant health burden worldwide. NAFLD includes a broad range of conditions, including simple steatosis and nonalcoholic steatohepatitis (NASH) [1]. The pathophysiology of NASH is multifactorial, involving genetic and epigenetic factors, insulin resistance, adipose-derived hormones, and nutritional factors [2]. The most potent driver of NASH is lipotoxicity-induced hepatocyte death, which triggers inflammation and fibrosis, leading to cirrhosis or liver cancer. Women have an increased risk of insulin resistance, hyperlipidemia, and visceral fat accumulation, all of which are known risk factors of NAFLD [3]. A higher incidence of NAFLD is found in postmenopausal women than in premenopausal women, as estrogen inhibits stellate cell activation and fibrogenesis, suggesting a correlation with the progression of NAFLD/NASH [4]

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