Bariatric surgery-induced weight loss reduces hepatic lipid peroxidation levels and affects hepatic cytochrome P-450 protein content

Lauren N. Bell, Constance J. Temm, Rashmil Saxena, Raj Vuppalanchi, Philip Schauer, Mordechai Rabinovitz, Alyssa Krasinskas, Naga Chalasani, Samer G. Mattar

Research output: Contribution to journalArticle

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Abstract

Objective: To evaluate the effects of surgical weight loss on hepatic lipid peroxidation levels and cytochrome P-450 protein expression in patients with nonalcoholic fatty liver disease (NAFLD). Summary background data: NAFLD and nonalcoholic steatohepatitis (NASH) affect hepatic cytochrome P-450 (CYP) protein expression and activity, and CYP2E1 may play a role in the pathogenesis of NAFLD and NASH through induction of oxidative stress and lipid peroxidation. NAFLD and NASH are associated with increased systemic lipid peroxidation levels and elevated hepatic CYP2E1 activity, but hepatic CYP3A4/5 activity is decreased. Methods: Liver biopsies from 20 patients with NAFLD who underwent bariatric surgery were obtained intraoperatively and at 15 ± 7 months following surgery. Hepatic malondialdehyde (MDA) levels (a marker of lipid peroxidation), CYP2E1 and CYP3A4/5 protein expression, and steatosis, as a percent of total area, were measured by immunohistochemistry followed by digital image quantitation. Results: Following weight loss, as reflected by reduced BMI (54 ± 9 vs. 37 ± 9 kg/m; P < 0.001), features of the metabolic syndrome, grade and stage of liver disease, and liver histology were all significantly improved (P < 0.01). Hepatic MDA staining (35 ± 18% vs. 23 ± 14%; P = 0.02), CYP2E1 protein content (68 ± 9% vs. 56 ± 11%; P < 0.001), and steatosis (17 ± 7% vs. 2 ± 3%; P < 0.001) were significantly reduced following weight loss. CYP3A4/5 protein content was unchanged (57 ± 13% vs. 55 ± 13%; P = 0.433). The reduction in lipid peroxidation was independently associated with changes in CYP2E1 protein expression after bariatric surgery (r = 0.477; P = 0.033). Conclusion: Elevations in hepatic lipid peroxidation and CYP2E1 expression that are seen in NAFLD improve significantly with weight loss induced by bariatric surgery.

Original languageEnglish
Pages (from-to)1041-1048
Number of pages8
JournalAnnals of Surgery
Volume251
Issue number6
DOIs
StatePublished - Jun 2010

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Bariatric Surgery
Cytochrome P-450 Enzyme System
Lipid Peroxidation
Weight Loss
Cytochrome P-450 CYP2E1
Liver
Cytochrome P-450 CYP3A
Proteins
Malondialdehyde
Non-alcoholic Fatty Liver Disease
Liver Diseases
Histology
Oxidative Stress
Immunohistochemistry
Staining and Labeling
Biopsy

ASJC Scopus subject areas

  • Surgery

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Bariatric surgery-induced weight loss reduces hepatic lipid peroxidation levels and affects hepatic cytochrome P-450 protein content. / Bell, Lauren N.; Temm, Constance J.; Saxena, Rashmil; Vuppalanchi, Raj; Schauer, Philip; Rabinovitz, Mordechai; Krasinskas, Alyssa; Chalasani, Naga; Mattar, Samer G.

In: Annals of Surgery, Vol. 251, No. 6, 06.2010, p. 1041-1048.

Research output: Contribution to journalArticle

Bell, Lauren N. ; Temm, Constance J. ; Saxena, Rashmil ; Vuppalanchi, Raj ; Schauer, Philip ; Rabinovitz, Mordechai ; Krasinskas, Alyssa ; Chalasani, Naga ; Mattar, Samer G. / Bariatric surgery-induced weight loss reduces hepatic lipid peroxidation levels and affects hepatic cytochrome P-450 protein content. In: Annals of Surgery. 2010 ; Vol. 251, No. 6. pp. 1041-1048.
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title = "Bariatric surgery-induced weight loss reduces hepatic lipid peroxidation levels and affects hepatic cytochrome P-450 protein content",
abstract = "Objective: To evaluate the effects of surgical weight loss on hepatic lipid peroxidation levels and cytochrome P-450 protein expression in patients with nonalcoholic fatty liver disease (NAFLD). Summary background data: NAFLD and nonalcoholic steatohepatitis (NASH) affect hepatic cytochrome P-450 (CYP) protein expression and activity, and CYP2E1 may play a role in the pathogenesis of NAFLD and NASH through induction of oxidative stress and lipid peroxidation. NAFLD and NASH are associated with increased systemic lipid peroxidation levels and elevated hepatic CYP2E1 activity, but hepatic CYP3A4/5 activity is decreased. Methods: Liver biopsies from 20 patients with NAFLD who underwent bariatric surgery were obtained intraoperatively and at 15 ± 7 months following surgery. Hepatic malondialdehyde (MDA) levels (a marker of lipid peroxidation), CYP2E1 and CYP3A4/5 protein expression, and steatosis, as a percent of total area, were measured by immunohistochemistry followed by digital image quantitation. Results: Following weight loss, as reflected by reduced BMI (54 ± 9 vs. 37 ± 9 kg/m; P < 0.001), features of the metabolic syndrome, grade and stage of liver disease, and liver histology were all significantly improved (P < 0.01). Hepatic MDA staining (35 ± 18{\%} vs. 23 ± 14{\%}; P = 0.02), CYP2E1 protein content (68 ± 9{\%} vs. 56 ± 11{\%}; P < 0.001), and steatosis (17 ± 7{\%} vs. 2 ± 3{\%}; P < 0.001) were significantly reduced following weight loss. CYP3A4/5 protein content was unchanged (57 ± 13{\%} vs. 55 ± 13{\%}; P = 0.433). The reduction in lipid peroxidation was independently associated with changes in CYP2E1 protein expression after bariatric surgery (r = 0.477; P = 0.033). Conclusion: Elevations in hepatic lipid peroxidation and CYP2E1 expression that are seen in NAFLD improve significantly with weight loss induced by bariatric surgery.",
author = "Bell, {Lauren N.} and Temm, {Constance J.} and Rashmil Saxena and Raj Vuppalanchi and Philip Schauer and Mordechai Rabinovitz and Alyssa Krasinskas and Naga Chalasani and Mattar, {Samer G.}",
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T1 - Bariatric surgery-induced weight loss reduces hepatic lipid peroxidation levels and affects hepatic cytochrome P-450 protein content

AU - Bell, Lauren N.

AU - Temm, Constance J.

AU - Saxena, Rashmil

AU - Vuppalanchi, Raj

AU - Schauer, Philip

AU - Rabinovitz, Mordechai

AU - Krasinskas, Alyssa

AU - Chalasani, Naga

AU - Mattar, Samer G.

PY - 2010/6

Y1 - 2010/6

N2 - Objective: To evaluate the effects of surgical weight loss on hepatic lipid peroxidation levels and cytochrome P-450 protein expression in patients with nonalcoholic fatty liver disease (NAFLD). Summary background data: NAFLD and nonalcoholic steatohepatitis (NASH) affect hepatic cytochrome P-450 (CYP) protein expression and activity, and CYP2E1 may play a role in the pathogenesis of NAFLD and NASH through induction of oxidative stress and lipid peroxidation. NAFLD and NASH are associated with increased systemic lipid peroxidation levels and elevated hepatic CYP2E1 activity, but hepatic CYP3A4/5 activity is decreased. Methods: Liver biopsies from 20 patients with NAFLD who underwent bariatric surgery were obtained intraoperatively and at 15 ± 7 months following surgery. Hepatic malondialdehyde (MDA) levels (a marker of lipid peroxidation), CYP2E1 and CYP3A4/5 protein expression, and steatosis, as a percent of total area, were measured by immunohistochemistry followed by digital image quantitation. Results: Following weight loss, as reflected by reduced BMI (54 ± 9 vs. 37 ± 9 kg/m; P < 0.001), features of the metabolic syndrome, grade and stage of liver disease, and liver histology were all significantly improved (P < 0.01). Hepatic MDA staining (35 ± 18% vs. 23 ± 14%; P = 0.02), CYP2E1 protein content (68 ± 9% vs. 56 ± 11%; P < 0.001), and steatosis (17 ± 7% vs. 2 ± 3%; P < 0.001) were significantly reduced following weight loss. CYP3A4/5 protein content was unchanged (57 ± 13% vs. 55 ± 13%; P = 0.433). The reduction in lipid peroxidation was independently associated with changes in CYP2E1 protein expression after bariatric surgery (r = 0.477; P = 0.033). Conclusion: Elevations in hepatic lipid peroxidation and CYP2E1 expression that are seen in NAFLD improve significantly with weight loss induced by bariatric surgery.

AB - Objective: To evaluate the effects of surgical weight loss on hepatic lipid peroxidation levels and cytochrome P-450 protein expression in patients with nonalcoholic fatty liver disease (NAFLD). Summary background data: NAFLD and nonalcoholic steatohepatitis (NASH) affect hepatic cytochrome P-450 (CYP) protein expression and activity, and CYP2E1 may play a role in the pathogenesis of NAFLD and NASH through induction of oxidative stress and lipid peroxidation. NAFLD and NASH are associated with increased systemic lipid peroxidation levels and elevated hepatic CYP2E1 activity, but hepatic CYP3A4/5 activity is decreased. Methods: Liver biopsies from 20 patients with NAFLD who underwent bariatric surgery were obtained intraoperatively and at 15 ± 7 months following surgery. Hepatic malondialdehyde (MDA) levels (a marker of lipid peroxidation), CYP2E1 and CYP3A4/5 protein expression, and steatosis, as a percent of total area, were measured by immunohistochemistry followed by digital image quantitation. Results: Following weight loss, as reflected by reduced BMI (54 ± 9 vs. 37 ± 9 kg/m; P < 0.001), features of the metabolic syndrome, grade and stage of liver disease, and liver histology were all significantly improved (P < 0.01). Hepatic MDA staining (35 ± 18% vs. 23 ± 14%; P = 0.02), CYP2E1 protein content (68 ± 9% vs. 56 ± 11%; P < 0.001), and steatosis (17 ± 7% vs. 2 ± 3%; P < 0.001) were significantly reduced following weight loss. CYP3A4/5 protein content was unchanged (57 ± 13% vs. 55 ± 13%; P = 0.433). The reduction in lipid peroxidation was independently associated with changes in CYP2E1 protein expression after bariatric surgery (r = 0.477; P = 0.033). Conclusion: Elevations in hepatic lipid peroxidation and CYP2E1 expression that are seen in NAFLD improve significantly with weight loss induced by bariatric surgery.

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