AJM Online

Clinical communication to the Editor

Severe Hepatic Injury Caused by Orlistat

Orlistat is a tetrahydrolipstatin, which inhibits both pancreatic and gastric lipase enzymes in the gut and prevents the absorption of dietary fats in the intestine. Therefore, it is widely used as an anti-obesity medication to control and manage body weight in obese patients worldwide. Despite this, the mounting number of clinical studies report that orlistat treatment induces adverse effects like pancreatitis, hepatic failure, kidney stone, acute oxalate nephropathy, and others. Although various factors could mediate the adverse effects of orlistat, emerging shreds of evidence suggest that genetic polymorphism-associated factors could be the primary reason for the cause. Hence, in this review, we first collated the most critical clinical adverse effects caused by orlistat and then appraised the susceptible genetic polymorphism that could further worsen the adverse effects of orlistat. Nonetheless, this review warrants similar conceptual approaches to understand orlistat's adverse effects in the selective genetic polymorphism and improve the therapeutic outcome of orlistat.

The mulberry (Morus alba L.) is a plant that mainly grows in East Asian countries such as Korea and China and has been used as a folk remedy for improving inflammation, cancer, and diabetes. Ramulus mori, the twig of Morus alba L., is known as “sangzhi” or “ppongnamugazhi” in Korea and used as a traditional medicine. Moreover, its effective compounds show some health benefits such as cholesterol reduction and attenuation of acute colitis.

As the number of obese people is increasing worldwide, the demand for diet drugs or products to treat obesity is also increasing. In this study, we investigated the antiobesity effect of the ethanolic extract of Ramulus mori (ERM) using differentiated 3T3-L1 adipocytes and a high-fat diet (HFD)-induced obese mouse model.

The expression levels of genes and proteins related to adipogenesis, lipogenesis, and lipolysis were analyzed by quantitative real-time PCR (qPCR) and western blot, respectively. Oil red O staining was carried out to determine the amount of neutral lipids deposited in the liver.

Compared with the ERM-untreated group, the ERM-treated groups exhibited reduced expression levels of genes involved in adipogenesis and lipogenesis in differentiated adipocytes and in HFD-induced obese mice, while the expression levels of genes involved in lipolysis increased. The administration of ERM to HFD-induced obese mice reduced the body weight, liver weight, and epididymal adipose tissue weight. Compared with the untreated HFD-induced obese mice, the ERM-treated mice exhibited decreased serum lipid levels. ERM treatment also reduced lipid accumulation in the liver, which was confirmed by oil red O staining.

ERM has the potential to be an effective natural material for reducing obesity.

En los últimos años ha aparecido un considerable número de publicaciones en la literatura médica sobre la hepatotoxicidad asociada a productos herbarios a los que se ha atribuido un efecto adelgazante. La expresión clínica de hepatotoxicidad ha oscilado entre cuadros de hepatitis autolimitada, indistinguibles de los causados por los virus de la hepatitis, hasta formas de hepatitis fulminante que han causado muerte o han requerido un trasplante hepático. Estos productos, que se venden como productos dietéticos o suplementos dietéticos, no pasan los controles de seguridad a que se somete a los fármacos antes de su comercialización, por lo que la prevención de sus efectos tóxicos exige un mejor conocimiento del público para que evite su empleo, ya que sus beneficios nunca han sido comprobados, y una actuación decidida de los médicos para que contribuyan a disuadir de su empleo a sus pacientes. Una regulación estricta de la autorización de la comercialización de todos estos productos, denominados naturales, es muy necesaria para minimizar los daños que pueden causar.

In the last few years, a considerable number of reports have been published on hepatotoxicity associated with herbal products attributed with weight-reducing properties. Clinical expression of hepatotoxicity has ranged from symptoms of self-limiting hepatitis, indistinguishable from those caused by the hepatitis viruses, to forms of fulminant hepatitis causing death or requiring liver transplantation. These products, which are sold as dietary products or supplements, do not undergo the safety tests required of drugs before their release on to the market. To prevent the toxic effects of herbal products, the general public should be made aware of their harmful effects and – since the benefits of these products have not been demonstrated – avoid their use, while physicians should strongly discourage patients from taking these products. Authorization of the commercialization of all these “natural” products should be strictly regulated to minimize the harm they can cause.