Cargando…

Therapeutic reduction of lysophospholipids in the digestive tract recapitulates the metabolic benefits of bariatric surgery and promotes diabetes remission

OBJECTIVE: Obesity and obesity-related metabolic disorders are major health problems worldwide. The most effective obesity intervention is bariatric surgery. This study tested the hypothesis that bariatric surgery alters phospholipid metabolism in the gastrointestinal tract to favor a metabolically...

Descripción completa

Detalles Bibliográficos
Autores principales: Cash, James G., Konaniah, Eddy, Hegde, Narasimha, Kuhel, David G., Watanabe, Miki, Romick-Rosendale, Lindsey, Hui, David Y.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6158127/
https://www.ncbi.nlm.nih.gov/pubmed/30087032
http://dx.doi.org/10.1016/j.molmet.2018.07.009
_version_ 1783358368128172032
author Cash, James G.
Konaniah, Eddy
Hegde, Narasimha
Kuhel, David G.
Watanabe, Miki
Romick-Rosendale, Lindsey
Hui, David Y.
author_facet Cash, James G.
Konaniah, Eddy
Hegde, Narasimha
Kuhel, David G.
Watanabe, Miki
Romick-Rosendale, Lindsey
Hui, David Y.
author_sort Cash, James G.
collection PubMed
description OBJECTIVE: Obesity and obesity-related metabolic disorders are major health problems worldwide. The most effective obesity intervention is bariatric surgery. This study tested the hypothesis that bariatric surgery alters phospholipid metabolism in the gastrointestinal tract to favor a metabolically healthy gut microbiota profile and therapeutic intervention of phospholipid metabolism in the gastrointestinal may have similar metabolic benefits. METHODS: The first study compared plasma levels of the bioactive lipid metabolites lysophospholipid and trimethylamine N-oxide (TMAO) as well as gut microbiota profile in high fat/carbohydrate (HFHC) diet-fed C57BL/6 mice with or without vertical sleeve gastrectomy (VSG) and in Pla2g1b(−/−) mice with group 1B phospholipase A(2) gene inactivation. The second study examined the effectiveness of the non-absorbable secretory phospholipase A(2) inhibitor methyl indoxam to reverse hyperglycemia and hyperlipidemia in HFHC diet-fed C57BL/6 mice after diabetes onset. RESULTS: Both bariatric surgery and PLA2G1B inactivation were shown to reduce lysophospholipid content in the gastrointestinal tract, resulting in resistance to HFHC diet-induced alterations of the gut microbiota, reduction of the cardiovascular risk factors hyperlipidemia and TMAO, decreased adiposity, and prevention of HFHC diet-induced diabetes. Importantly, treatment of wild type mice with methyl indoxam after HFHC diet-induced onset of hyperlipidemia and hyperglycemia effectively restored normal plasma lipid and glucose levels and replicated the metabolic benefits of VSG surgery with diabetes remission and TMAO reduction. CONCLUSION: These results provided pre-clinical evidence that PLA2G1B inhibition in the digestive tract may be a viable alternative option to bariatric surgery for obesity and obesity-related cardiometabolic disorder intervention.
format Online
Article
Text
id pubmed-6158127
institution National Center for Biotechnology Information
language English
publishDate 2018
publisher Elsevier
record_format MEDLINE/PubMed
spelling pubmed-61581272018-09-27 Therapeutic reduction of lysophospholipids in the digestive tract recapitulates the metabolic benefits of bariatric surgery and promotes diabetes remission Cash, James G. Konaniah, Eddy Hegde, Narasimha Kuhel, David G. Watanabe, Miki Romick-Rosendale, Lindsey Hui, David Y. Mol Metab Original Article OBJECTIVE: Obesity and obesity-related metabolic disorders are major health problems worldwide. The most effective obesity intervention is bariatric surgery. This study tested the hypothesis that bariatric surgery alters phospholipid metabolism in the gastrointestinal tract to favor a metabolically healthy gut microbiota profile and therapeutic intervention of phospholipid metabolism in the gastrointestinal may have similar metabolic benefits. METHODS: The first study compared plasma levels of the bioactive lipid metabolites lysophospholipid and trimethylamine N-oxide (TMAO) as well as gut microbiota profile in high fat/carbohydrate (HFHC) diet-fed C57BL/6 mice with or without vertical sleeve gastrectomy (VSG) and in Pla2g1b(−/−) mice with group 1B phospholipase A(2) gene inactivation. The second study examined the effectiveness of the non-absorbable secretory phospholipase A(2) inhibitor methyl indoxam to reverse hyperglycemia and hyperlipidemia in HFHC diet-fed C57BL/6 mice after diabetes onset. RESULTS: Both bariatric surgery and PLA2G1B inactivation were shown to reduce lysophospholipid content in the gastrointestinal tract, resulting in resistance to HFHC diet-induced alterations of the gut microbiota, reduction of the cardiovascular risk factors hyperlipidemia and TMAO, decreased adiposity, and prevention of HFHC diet-induced diabetes. Importantly, treatment of wild type mice with methyl indoxam after HFHC diet-induced onset of hyperlipidemia and hyperglycemia effectively restored normal plasma lipid and glucose levels and replicated the metabolic benefits of VSG surgery with diabetes remission and TMAO reduction. CONCLUSION: These results provided pre-clinical evidence that PLA2G1B inhibition in the digestive tract may be a viable alternative option to bariatric surgery for obesity and obesity-related cardiometabolic disorder intervention. Elsevier 2018-07-26 /pmc/articles/PMC6158127/ /pubmed/30087032 http://dx.doi.org/10.1016/j.molmet.2018.07.009 Text en © 2018 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Original Article
Cash, James G.
Konaniah, Eddy
Hegde, Narasimha
Kuhel, David G.
Watanabe, Miki
Romick-Rosendale, Lindsey
Hui, David Y.
Therapeutic reduction of lysophospholipids in the digestive tract recapitulates the metabolic benefits of bariatric surgery and promotes diabetes remission
title Therapeutic reduction of lysophospholipids in the digestive tract recapitulates the metabolic benefits of bariatric surgery and promotes diabetes remission
title_full Therapeutic reduction of lysophospholipids in the digestive tract recapitulates the metabolic benefits of bariatric surgery and promotes diabetes remission
title_fullStr Therapeutic reduction of lysophospholipids in the digestive tract recapitulates the metabolic benefits of bariatric surgery and promotes diabetes remission
title_full_unstemmed Therapeutic reduction of lysophospholipids in the digestive tract recapitulates the metabolic benefits of bariatric surgery and promotes diabetes remission
title_short Therapeutic reduction of lysophospholipids in the digestive tract recapitulates the metabolic benefits of bariatric surgery and promotes diabetes remission
title_sort therapeutic reduction of lysophospholipids in the digestive tract recapitulates the metabolic benefits of bariatric surgery and promotes diabetes remission
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6158127/
https://www.ncbi.nlm.nih.gov/pubmed/30087032
http://dx.doi.org/10.1016/j.molmet.2018.07.009
work_keys_str_mv AT cashjamesg therapeuticreductionoflysophospholipidsinthedigestivetractrecapitulatesthemetabolicbenefitsofbariatricsurgeryandpromotesdiabetesremission
AT konaniaheddy therapeuticreductionoflysophospholipidsinthedigestivetractrecapitulatesthemetabolicbenefitsofbariatricsurgeryandpromotesdiabetesremission
AT hegdenarasimha therapeuticreductionoflysophospholipidsinthedigestivetractrecapitulatesthemetabolicbenefitsofbariatricsurgeryandpromotesdiabetesremission
AT kuheldavidg therapeuticreductionoflysophospholipidsinthedigestivetractrecapitulatesthemetabolicbenefitsofbariatricsurgeryandpromotesdiabetesremission
AT watanabemiki therapeuticreductionoflysophospholipidsinthedigestivetractrecapitulatesthemetabolicbenefitsofbariatricsurgeryandpromotesdiabetesremission
AT romickrosendalelindsey therapeuticreductionoflysophospholipidsinthedigestivetractrecapitulatesthemetabolicbenefitsofbariatricsurgeryandpromotesdiabetesremission
AT huidavidy therapeuticreductionoflysophospholipidsinthedigestivetractrecapitulatesthemetabolicbenefitsofbariatricsurgeryandpromotesdiabetesremission