Hepatotoxicity of Drugs Used for Treatment of Obesity and Its Comorbidities

Ghali, Peter; Lindor, Keith D.

doi:10.1055/s-2004-860868

Cited by 14 publications

(4 citation statements)

References 89 publications

(135 reference statements)

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“…COS and UAOS markedly decreased the liver fat and fat vacuole size induced by HFD. Liver injury and hepatotoxicity are the two main factors for hyperlipidemia and obesity [37,38]. To further check the hepatoprotective effect of UAOS, serum AST and ALT levels were measured (Figure 4F,G).…”

Section: Resultsmentioning

confidence: 99%

Efficiently Anti-Obesity Effects of Unsaturated Alginate Oligosaccharides (UAOS) in High-Fat Diet (HFD)-Fed Mice

Wang

2019

Marine Drugs

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Obesity and its related complications have become one of the leading problems affecting human health. However, current anti-obesity treatments are limited by high cost and numerous adverse effects. In this study, we investigated the use of a non-toxic green food additive, known as unsaturated alginate oligosaccharides (UAOS) from the enzymatic degradation of Laminaria japonicais, which showed effective anti-obesity effects in a high-fat diet (HFD) mouse model. Compared with acid hydrolyzed saturated alginate oligosaccharides (SAOS), UAOS significantly reduced body weight, serum lipid, including triacylglycerol (TG), total cholesterol (TC) and free fatty acids (FFA), liver weight, liver TG and TC, serum alanine aminotransferase (ALT), and aspartate aminotransferase (AST) levels, adipose mass, reactive oxygen species (ROS) formation, and accumulation induced in HFD mice. Moreover, the structural differences in β-d-mannuronate (M) and its C5 epimer α-l-guluronate (G) did not cause significant functional differences. Meanwhile, UAOS significantly increased both AMP-activated protein kinase α (AMPKα) and acetyl-CoA carboxylase (ACC) phosphorylation in adipocytes, which indicated that UAOS had an anti-obesity effect mainly through AMPK signaling. Our results indicate that UAOS has the potential for further development as an adjuvant treatment for many metabolic diseases such as fatty liver, hypertriglyceridemia, and possibly diabetes.

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Section: Resultsmentioning

confidence: 99%

Efficiently Anti-Obesity Effects of Unsaturated Alginate Oligosaccharides (UAOS) in High-Fat Diet (HFD)-Fed Mice

Wang

2019

Marine Drugs

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“…In addition, concerns persist about the risks of potential toxicity for many proposed therapeutic agents in the absence of proven benefit. 43 These issues have led to the widespread recommendation of weight loss, principally through lifestyle changes such as diet and exercise, as the mainstays of NAFLD treatment (e.g, [44][45][46] ). However, as a recent comprehensive review demonstrated, even evidence that weight loss achieved by these safe and conservative methods is of benefit to NAFLD is inconclusive.…”

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confidence: 99%

Role of Fatty Acids in the Pathogenesis of Obesity and Fatty Liver: Impact of Bariatric Surgery

Verna

Berk

2008

Semin Liver Dis

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Nonalcoholic fatty liver disease (NAFLD) spans a spectrum from simple steatosis to nonalcoholic steatohepatitis (NASH) to cirrhosis. Simple steatosis is the substrate upon which the more serious entities in the spectrum develop; it is the first ''hit'' in the multistep pathogenesis of NASH, which is considered the hepatic manifestation of the metabolic syndrome. Demonstration of the existence of regulatable fatty acid transport mechanisms has contributed to clarifying the role of fatty acid disposition in obesity, the various components of NAFLD, and the metabolic syndrome. Hepatic steatosis is closely linked to obesity. This linkage is based on the fact that obesity results in marked enlargement of the intraabdominal visceral fat depots. The eventual development of insulin resistance leads to continuous lipolysis within these depots, releasing fatty acids into the portal circulation, where they are rapidly translocated to the liver and reassembled into triglycerides. Reactive oxygen species, generated in the liver from oxidation of fatty acids, are precipitating factors in the cascade of events leading from simple steatosis to NASH. Dysregulation of fatty acid disposition, with ectopic lipid accumulation in other tissues, is a major contributing factor to other components of the metabolic syndrome. Bariatric surgery is an effective treatment for severe obesity, but its role in the management of the various forms of fatty liver disease is unclear. Our review of the literature that includes both initial and follow-up liver biopsies suggests that most obese patients with simple steatosis and NASH who undergo bariatric surgery will achieve improvement in hepatic histology, but that occasional patients, especially those who lose weight very rapidly, may show worsening of either fibrosis or steatohepatitis.

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“…resistance (16). Furthermore, sulfonylurea drugs and α-glucosidase inhibitors have also been reported to cause hepatotoxicity and so their use is restricted (14,17). It has been reported that nateglinide can be safely used because it causes no hepatotoxicity (9).…”

Section: Discussionmentioning

confidence: 98%