Association of the PNPLA2, SCD1 and Leptin Expression with Fat Distribution in Liver and Adipose Tissue From Obese Subjects.

The expansion of adipose tissue is regulated by insulin and leptin through sterol regulatory element-binding protein-1c (SREBP-1c), up-regulating lipogenesis in tissues by Stearoylcoenzyme A desaturase 1 (SCD1) enzyme, while adipose triglyceride lipase (ATGL) enzyme is key in lipolysis. The research objective was to evaluate the expression of Sterol Regulatory Element Binding Transcription Factor 1 (SREBF1), SCD1, Patatin Like Phospholipase Domain Containing 2 (PNPLA2), and leptin (LEP) genes in hepatic-adipose tissue, and related them with the increment and distribution of fat depots of individuals without insulin resistance. Thirty-eight subjects undergoing elective cholecystectomy with liver and adipose tissue biopsies (subcutaneous-omental) are included. Tissue gene expression was assessed by qPCR and biochemical parameters determined. Individuals are classified according to the body mass index, classified as lean (control group, n=12), overweight (n=11) and obesity (n=15). Abdominal adiposity was determined by anthropometric and histopathological study of the liver. Increased SCD1 expression in omental adipose tissue (p=0.005) and PNPLA2 in liver (p=0.01) were found in the obesity group. PNPLA2 decreased expression in subcutaneous adipose tissue was significant in individuals with abdominal adiposity (p=0.017). Anthropometric parameters positively correlated with liver PNPLA2 and the expression of liver PNPLA2 with serum leptin. SCD1 increased levels may represent lipid storage activity in omental adipose tissue. Liver PNPLA2 increased expression could function as a primary compensatory event of visceral fat deposits associated to the leptin hormone related to the increase of adipose tissue.

Expression of the receptor of advanced glycation end-products (RAGE) and membranal location in peripheral blood mononuclear cells (PBMC) in obesity and insulin resistance.

OBJECTIVES: The present study aimed to evaluate the receptor of advanced glycation end-products (RAGE), NF-kB, NRF2 gene expression, and RAGE cell distribution in peripheral blood mononuclear cells (PBMC) in subjects with obesity and IR compared with healthy subjects. MATERIALS AND METHODS: The mRNA expression levels of RAGE, NF-kB, NRF2, and GAPDH were determined in PBMC by qPCR in 20 obese (OB), 17 obese with insulin resistance (OB-IR), and 20 healthy subjects (HS), matched by age and sex. RAGE protein expression and its localization were determined by Western Blot and immunocytochemistry (ICC) analysis, total soluble RAGE (sRAGE) and MCP-1 plasma levels by ELISA. RESULTS: RAGE, NF-kB, and NRF2 genes mRNA expression in PBMCs did not show variation between groups. RAGE protein was lower in OB and OB-IR groups; RAGE was located predominantly on the cell-surface in the OB-IR group compared to the HS group (22% vs 9.5%, P<0.001). OB-IR group showed lower sRAGE plasma levels, and correlated negatively with HOMA-IR, ALT parameters (r= -0.374, r= -0.429, respectively), and positively with NFE2L2 mRNA (r= 0.540) P<0.05. CONCLUSION: In this study, OB-IR subjects did not reflect significant differences in gene expression; however, correlations detected between sRAGE, biochemical parameters, and NRF2, besides the predominant RAGE distribution on the cell membrane in PBMC could be evidence of the early phase of the inflammatory cascade and the subsequent damage in specific tissues in subjects with OB-IR.

Association of -319 C/T and +49 A/G polymorphisms of CTLA-4 gene in patients with hepatitis C virus infection. / Asociación de los polimorfismos −319 C/T y +49 A/G del gen CTLA-4 en pacientes con infección por el virus de la hepatitis C.

INTRODUCTION AND OBJECTIVE: Molecular changes in the CTLA-4 gene can modify the ability to control T lymphocyte proliferation, and promote the persistence or elimination of the hepatitis C virus (HCV). We aimed to investigate the frequency and association of -319 C/T and +49 A/G polymorphism in the CTLA-4 gene in patients infected with HCV. METHODS: The CTLA-4 gene polymorphisms (-319 C/T in the promoter region, and +49 A/G in exon 1) were analysed by T-ARMS-PCR in 420 individuals, including 205 chronic HCV infected patients and 215 healthy subjects. RESULTS: We found a positive association of +49G allele with HCV infection (OR 1.48; 95% CI 1.09-2.02; p=.02), and with males (OR 1.80; 95% CI 1.16-2.79; p=.02), both in chronic disease (without cirrhosis). Also, significant differences in +49 A/G genotypes distribution between HCV infected patients and healthy subjects were shown in a dominant genetic model (GG+GA versus AA; OR 1.57; 95% CI 1.05-2.33; p=.04). No significant differences were observed in the -319 C/T polymorphism between HCV infected patients and healthy subjects. Moreover, -319C/+49G haplotype confers susceptibility to HCV genotype 3 infection (OR 10.68; 95% CI 1.17-96.97; p=.04). CONCLUSIONS: The +49G allele confers susceptibility to HCV infection and with male gender, both in chronic disease. In addition, the -319C/+49G haplotype confers susceptibility to HCV genotype 3 infection. Our results support an important role of the -319 C/T and +49 A/G polymorphisms in HCV infection.

Granulomatous hypophysitis by Mycobacterium gordonae in a non HIV-infected patient.

Lymphocytic or granulomatous hypophysitis is a rare entity with a difficult diagnosis. Our objective was to report a patient with non-tuberculous granulomatous hypophysitis. An HIV-negative 45-year old man with confusional state, subacute ophthalmoplegia, and clinical and laboratory findings of panhypopituitarism was seen in the emergency unit. A cranial MRI showed a sellar mass suggestive of hypophysitis. After an unsuccessful attempt with steroids and antituberculous drugs the patient died. Post-mortem histopathology revealed granulomatous lesions and restriction fragment length polymorphism analysis confirmed the presence of Mycobacterium gordonae's DNA. In conclusion, we should consider granulomatous hypophysitis in the differential diagnosis of non-secreting hypophyseal tumors. The etiology of a pituitary granuloma by a non-tuberculous mycobacteria is best reached by histopathological techniques and molecular assays. The optimal therapy is yet to be established.