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- Baumeier, Christian, et al.
(författare)
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Hepatic DPP4 DNA methylation associates with fatty liver
- 2017
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Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 66:1, s. 25-35
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Tidskriftsartikel (refereegranskat)abstract
- Hepatic DPP4 expression is elevated in subjects with ectopic fat accumulation in the liver. However, whether increased dipeptidyl peptidase 4 (DPP4) is involved in the pathogenesis or is rather a consequence ofmetabolic disease is not known. We therefore studied the transcriptional regulation of hepatic Dpp4 in young mice prone to diet-induced obesity. Already at 6 weeks of age, expression of hepatic Dpp4 was increased in mice with high weight gain, independent of liver fat content. In the same animals, methylation of four intronic CpG sites was decreased, amplifying glucose-induced transcription of hepatic Dpp4. In older mice, hepatic triglyceride content was increased only in animals with elevated Dpp4 expression. Expression and release of DPP4 were markedly higher in the liver compared with adipose depots. Analysis of human liver biopsy specimens revealed a correlation of DPP4 expression and DNA methylation to stages of hepatosteatosis and nonalcoholic steatohepatitis. In summary, our results indicate a crucial role of the liver in participation to systemic DPP4 levels. Furthermore, the data show that glucoseinduced expression of Dpp4 in the liver is facilitated by demethylation of the Dpp4 gene early in life. This might contribute to early deteriorations in hepatic function, which in turn result in metabolic disease such as hepatosteatosis later in life.
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| 2. |
- Neff, Karl J., et al.
(författare)
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Renal Function and Remission of Hypertension After Bariatric Surgery: a 5-Year Prospective Cohort Study
- 2017
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Ingår i: Obesity Surgery. - : Springer Science and Business Media LLC. - 0960-8923 .- 1708-0428. ; 27, s. 613-619
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Tidskriftsartikel (refereegranskat)abstract
- © 2016, Springer Science+Business Media New York. Purpose: This study examines the effect of Roux-en-Y gastric bypass (RYGB) and laparoscopic adjustable gastric banding (LAGB) on renal function for at least 5years post-operatively in a tertiary referral center for bariatric surgery. Materials and Methods: This prospective cohort study of patients undergoing RYGB and LAGB measured renal function, blood pressure, and diabetes status pre-operatively and then 1 and 5years post-operatively. Renal function was assessed using the Modification of Diet in Renal Disease (MDRD), Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), and Cockcroft-Gault formulae. Hypertension and diabetes were defined by the European Society of Hypertension and European Society of Cardiology joint guidelines and American Diabetes Association guidelines, respectively. A sub-group who had completed 10years post-operative follow-up was also included. Results: Estimated glomerular filtration rate (eGFR) increased over 5years after RYGB (N = 190; 94 ± 2mL/min/1.73m2 to 102 ± 22mL/min/1.73m2, p = 0.01) and LAGB (N = 271; 88 ± 1 to 93 ± 22mL/min/1.73m2, p = 0.02). In a sub-group with up to 10years post-operative date, this trend was maintained. In patients with renal impairment, eGFR improved over 5years (52 ± 2 to 68 ± 7mL/min/1.73m2, p = 0.01). Remission of hypertension was greater after RYGB than LAGB at 1year (32 vs. 16%, p = 0.008) and at 5years post-operatively (23 vs. 11%, p = 0.02). Conclusions: Bariatric surgery stabilizes eGFR post-operatively for at least 5years. In a sub-group with renal impairment, eGFR is increased in the first post-operative year and this is maintained for up to 5years. RYGB is an effective procedure in achieving blood pressure control.
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