Inhibition of intestinal cholesterol absorption by ezetimibe is a novel therapeutic target for fatty liver

Ezetimibe is a novel lipid-lowering agent that inhibits intestinal absorption of dietary and biliary cholesterol. The effects of ezetimibe on low-density lipoprotein (LDL)-cholesterol were found to generally consistent across all subgroups analyzed, including baseline lipid profile, hypertension, diabetes mellitus, and body mass index. Furthermore, recent clinical studies also revealed that co-administration of ezetimibe with on-going statins offered a well-tolerated and efficacious treatment to lower LDL-cholesterol levels in hypercholesterolemic patients with diabetes mellitus or the metabolic syndrome. Niemann-Pick C1 like 1 (NPC1L1) protein is recently found to be critical for intestinal cholesterol absorption, and is a target protein for ezetimibe. Human NPC1L1 protein is predominantly expressed in liver, whereas small intestine expression is only about 2-4% of that found in the liver. Thus, NPC1L1 does not function solely in the intestinal cholesterol absorption. Furthermore, loss of NPC1L1 expression has been shown to protect against diet-induced fatty liver. These observations let us to speculate that ezetimibe will become a new therapeutic approach for the treatment of non-alcoholic fatty liver, the hepatic manifestation of insulin resistant patients with the metabolic syndrome. In this paper, we would like to propose the possible ways of testing our hypothesis as follows. (1) Does ezetimibe treatment improve fatty liver in patients with hypercholesterolemia or the metabolic syndrome? If the answers are yes, are these beneficial effects of ezetimibe superior to those of other anti-hyperlipidemic resins with equihypolipidemic properties? (2) Does ezetimibe treatment improve insulin sensitivity in fatty liver patients with the metabolic syndrome? (3) How about the effects of ezetimibe treatment on serum levels of adiponectin, a key adipokine with insulin-sensitizing property? Large clinical trials will provide us with more definite information whether ezetimibe treatment can improve fatty liver and resultantly reduce the risk of progression of liver diseases in patients with the metabolic syndrome.     

Endogenous lipid pneumonia in a dog

Endogenous lipid pneumonia has previously been diagnosed in dogs only once. This report describes a case in a dog with a persistent cough, in which the histological diagnosis was based on the presence of numerous foamy macrophages that filled the alveoli and contained small sudanophilic vacuoles. The appearance of endogenous lipid pneumonia in this animal was accompanied by Dirofilaria immitis infection and chronic bronchitis.     

Relationship between intestinal motility and absorption. Electromyographic study in the dog. (author's transl)]

The effects of different food components on intestinal motility were studied by means of an electromyographic technique. The electrical activity of the small intestine in the fasted state consists of a cyclic recurring phenomenon - the myoelectric complex - which is inhibited by feeding. The duration of inhibition of the myoelectric complex was shown to depend on the nature of the food components (glucose, peptides or lipids) as well as on the caloric load. In the opposite, the intensity of the intestinal motility was seen to depend only on the nature of the food components, and not on the caloric load. Thus, the duration of inhibition of themyoelectric complex can be considered as a consistent and objective parameter, which reflects the duration of the fed state.