Hepatic function and the cardiometabolic syndrome

Abstract

Despite skeletal muscle being considered by many as the source of insulin resistance, physiology tells us that the liver is a central and cardinal regulator of glucose homeostasis. This is sometimes underestimated because, in contrast with muscle, investigations of liver function are technically very difficult. Nevertheless, recent experimental and clinical research has demonstrated clearly that, due in part to its anatomic position, the liver is exquisitely sensitive to insulin and other hormonal and neural factors, either by direct intrahepatic mechanisms or indirectly by organ cross-talk with muscle or adipose tissue. Because the liver receives absorbed nutrients, these have a direct impact on liver function, whether via a caloric excess or via the nature of food components (eg, fructose, many lipids, and trans fatty acids). An emerging observation with a possibly great future is the increase in intestinal permeability observed as a consequence of high fat intake or bacterial modifications in microbiota, whereby substances normally not crossing the gut gain access to the liver, where inflammation, oxidative stress, and lipid accumulation leads to fatty liver, a situation observed very early in the development of diabetes. The visceral adipose tissue located nearby is another main source of inflammatory substances and oxidative stress, and also acts on hepatocytes and Kupffer cells, resulting in stimulation of macrophages. Liberation of these substances, in particular triglycerides and inflammation factors, into the circulation leads to ectopic fat deposition and vascular damage. Therefore, the liver is directly involved in the development of the prediabetic cardiometabolic syndrome. Treatments are mainly metformin, and possibly statins and vitamin D. A very promising avenue is treatment of the leaky gut, which appears increasingly to be an important causal factor in hepatic insulin resistance and steatosis.

Effects of haloperidol and clozapine administration on oxidative stress in rat brain, liver and serum

“…dysregulation caused by clozapine than haloperidol [28]. These effects are likely mediated by changes in hepatic glucose output [29], and would be consistent with the large literature in Type 2 Diabetes Mellitus, which indicates a key role for hepatic oxidative stress in the onset of insulin resistance [30]. Also, transient elevations in liver enzymes have been reported in patients taking clozapine, and to a lesser degree haloperidol [31], while case reports indicate that hepatotoxicity may occur following clozapine treatment [22].…”

Triglyceride is strongly associated with nonalcoholic fatty liver disease among markers of hyperlipidemia and diabetes

“…The data indicated that TG was more closely associated with NAFLD than BG and HbA1c. Therefore, this may indicate that a diet high in carbohydrates may result in increased TG accumulation in hepatocytes (25,26). In conclusion, elevated TG was a marker of NAFLD.…”

Green tea polyphenol epigallocatechin-3-gallate ameliorates insulin resistance in non-alcoholic fatty liver disease mice

“…There fore, any transformation in hepatic insulin sensitivity is rapidly reflected in glucose homeostasis and TG levels [21] . Insulin resistance has been considered an important pathophysiologic mechanism of obesity, dyslipidemia, diabetes, hypertension and NAFLD [1,2] .…”