Background: Anderson's disease (AD) or chylomicron retention disease (CMRD) is a very rare hereditary lipid malabsorption syndrome. In order to discover novel mutations in the SAR1B gene and to evaluate the expression, as compared to healthy subjects, of the Sar1 gene and protein paralogues in the intestine, we investigated three previously undescribed individuals with the disease. Methods: The SAR1B, SAR1A and PCSK9 genes were sequenced. The expression of the SAR1B and SAR1A genes in intestinal biopsies of both normal individuals and patients was measured by RTqPCR. Immunohistochemistry using antibodies to recombinant Sar1 protein was used to evaluate the expression and localization of the Sar1 paralogues in the duodenal biopsies. Results: Two patients had a novel SAR1B mutation (p.Asp48ThrfsX17). The third patient, who had a previously described SAR1B mutation (p.Leu28ArgfsX7), also had a p.Leu21dup variant of the PCSK9 gene. The expression of the SAR1B gene in duodenal biopsies from an AD/CMRD patient was significantly decreased whereas the expression of the SAR1A gene was significantly increased, as compared to healthy individuals. The Sar1 proteins were present in decreased amounts in enterocytes in duodenal biopsies from the patients as compared to those from healthy subjects. Conclusions: Although the proteins encoded by the SAR1A and SAR1B genes are 90% identical, the increased expression of the SAR1A gene in AD/CMRD does not appear to compensate for the lack of the SAR1B protein. The PCSK9 variant, although reported to be associated with low levels of cholesterol, does not appear to exert any additional effect in this patient. The results provide further insight into the tissue-specific nature of AD/CMRD.

Summary: Background: Non‐alcoholic fatty liver disease (NAFLD) and viral hepatitis are associated with hepatic oxidative stress, which is partially dependent on the amount of hepatic fat.Aim: To determine whether the circulating lipid and oxidative stress parameters could be non‐invasive markers of hepatic steatosis.Methods: Sixty‐four patients with NAFLD or viral hepatitis were tested for lipid peroxidation products and antioxidant defence systems, lipid parameters and liver function tests.Results: Hepatic steatosis was correlated with lipids, γ‐glutamyltranspeptidase, thiobarbituric acid‐reactive substances, superoxide dismutase and superoxide dismutase/erythrocyte glutathione peroxidase ratio. γ‐Glutamyltranspeptidase, triglycerides and low‐density lipoprotein cholesterol were significantly higher in the presence of steatosis. No difference in blood oxidative stress markers was observed according to the presence or absence of steatosis except for the superoxide dismutase/erythrocyte glutathione peroxidase ratio. Total cholesterol, triglycerides and low‐density lipoprotein cholesterol were significantly higher in the NAFLD group (n = 17, 60% mean steatosis grade) than in the viral hepatitis group (n = 20, 13% mean steatosis grade). Only superoxide dismutase was lower and vitamin E higher in NAFLD than in viral hepatitis patients.Conclusions: Standard blood oxidative stress markers do not predict the extent of hepatic steatosis as they probably do not accurately reflect intrahepatic oxidative stress. Serum lipid levels were best correlated with hepatic steatosis.

Familial hypobetalipoproteinemia (FHBL) is an autosomal codominantly inherited disorder of lipoprotein metabolism characterized by decreased concentrations of low-density lipoprotein-cholesterol and of apolipoprotein B (apoB). Mutations of APOB gene lead to the formation of truncated forms of apoB. The study aimed at determining the truncated form of apoB responsible for FHBL associated with liver cirrhosis in a 27-year-old man. Analysis of the patient's lipoproteins has been performed by SDS-PAGE electrophoresis followed by immunoblotting with monoclonal antibodies. DNA of the family (proband, daughter, wife, father, and mother) was extracted, and PCR amplification was realized; amplicons were screened and sequenced. Electrophoresis allowed us to identify a truncated form of apoB (close to apoB 59%), associated with a new heterozygous apoB variant, 8402 C>G. This mutation creates a stop codon (TAC>TAG, Y2807X) and predicts to generate a truncated protein (apoB-61.9%). No other causes of cirrhosis were established by comprehensive clinical and biological investigations. We described here an unusual clinical observation of a patient with FHBL and early development of liver cirrhosis due to a new truncated form of apoB.

Obesity is associated with an oxidative stress status, defined as an excessive production of reactive oxygen species (ROS) compared to the level of antioxidants acting in the natural defence systems. Several sources of ROS can be identified in obesity (e.g., mitochondrial respiratory chain, or NADPH oxidase) and could contribute to the pathogenesis of obesity. Indeed, these conditions favour the development of insulin resistance and metabolic syndrome through deregulation of adipokines and pro-inflammatory cytokines, so that it could be of interest to associate antioxidant therapeutic strategies with strategies of weight loss. Among antioxidants, melatonin holds a special place, on the one hand for its antioxidant and anti-inflammatory properties, and on the other hand for its role as a metabolic regulator. As melatonin modulates several processes involved in obesity and its related metabolic alterations, it could have a therapeutic interest in the treatment of obesity.