Is obesity rather than the dietary supplement used for weight reduction the cause of liver injury?

Abstract

Acute liver injury has been attributed to dietary supplements (DS) used for weight loss, but their causal role was much questioned, and obesity as an alternative cause of the liver injury remained unclear. A comprehensive search of the Medline database was conducted with terms that included “DS,” “liver injury,” “obesity,” “obesity‐related liver diseases,” and “nonalcoholic steatohepatitis.” For each term, we focused on the first 50 publications. We undertook a manual search to identify additional reports. Underlying liver diseases and other health issues are common in patients taking DS for weight reduction. These include obesity or morbid obesity, as well as complex metabolic disorders complicated by excess morbidity and mortality due to associated liver diseases. Among these are nonalcoholic fatty liver disease with potential progression to nonalcoholic steatohepatitis and cirrhosis, often classified as cryptogenic with a rare risk of hepatocellular carcinoma. With the exception of hepatocellular carcinoma, these obesity‐related liver diseases were observed to varying degrees in patients, and some even required a liver transplant. This raises the question whether the liver injury that occurred in these patients is due to DS consumed for weight loss or to the underlying obesity‐related liver diseases. This analysis showed that, in many instances, the causal role of obesity has been neglected. Obesity‐associated liver diseases should be considered as differential diagnosis of liver injury in obese patients using DS.

Alcoholic Liver Disease: Alcohol Metabolism, Cascade of Molecular Mechanisms, Cellular Targets, and Clinical Aspects

“…Along with oxidative stress, there is a continuous generation of radicals including ROS by not only hepatocytes but also non-parenchymal cells and leucocytes (Figure 9). Because of incomplete intracellular oxygen splitting, radicals are part of common life in any healthy organism such as plants [277,278,279,280], animals [280], and humans [281,282]. ROS and the other reactive radicals are commonly scavenged by antioxidants and thereby detoxified.…”

“…ROS and the other reactive radicals are commonly scavenged by antioxidants and thereby detoxified. Disease occurs if these protective mechanisms are lacking, with obesity as a good example because radicals play an important role for many obesity-related co-morbidities [281]. ROS is also implicated in liver injury [282,283] including alcoholic liver disease [92,231,240] where various forms of ROS and reactive radicals are contributory (Table 5).…”

New Aspects of Lipotoxicity in Nonalcoholic Steatohepatitis

“…Lifestyle interventions can result in weight loss, decrease CVD, improve fibrosis, and delay the progress of T2DM [ 109 , 110 , 111 , 112 ]. Weight loss enhances the levels of aminotransferases and hepatic steatosis, as measured either by ultrasonography or magnetic resonance spectroscopy in proportion to the total quantity of weight lost [ 113 ].…”

Biochemical Aspects of the Hepatic Microsomal Ethanol-oxidizing System (MEOS): Resolved Initial Controversies and Updated Molecular Views

“…There is yet some uncertainty about the mechanisms of the CYP 2E1 increase and related gene expression upregulation caused by chronic alcohol consumption [52,[93][94][95][96]. For instance, prolonged alcohol use leads to an increased content of CYP 2E1 due to the transcription of the CYP 2E1 gene and occurs by a twostep mechanism [94] and when blood alcohol levels are high [93].…”

“…However, it has also been pointed out that increased CYP 2E1 levels are rarely accompanied by respective elevations of CYP 2E1 mRNA levels and may involve increases in gene transcription, mRNA translation, or protein stability against proteasome-mediated degradation [52]. Mechanisms of increased CYP 2E1 may be variable among the different diseases and conditions causing such increases unrelated to alcohol use [14,[95][96][97]. Of clinical interest are increased hepatic levels of CYP 2E1 observed in patients with obesity and associated nonalcoholic fatty liver disease, nonalcoholic steatohepatitis, diabetes mellitus, or the metabolic syndrome, as well as in fasting individuals [14].…”