Regulation of obesity-related insulin resistance with gut anti-inflammatory agents

Helen Luck, Sue Tsai, Jason Chung, Xavier Clemente-Casares, Magar Ghazarian, Xavier S. Revelo, Helena Lei, Cynthia T. Luk, Sally Yu Shi, Anuradha Surendra, Julia K. Copeland, Jennifer Ahn, David Prescott, Brittany A. Rasmussen, Melissa Hui Yen Chng, Edgar G. Engleman, Stephen E. Girardin, Tony K.T. Lam, Kenneth Croitoru, Shannon DunnDana J. Philpott, David S. Guttman, Minna Woo, Shawn Winer, Daniel A. Winer

Research output: Contribution to journalArticle

101 Citations (Scopus)

Abstract

Obesity has reached epidemic proportions, but little is known about its influence on the intestinal immune system. Here we show that the gut immune system is altered during high-fat diet (HFD) feeding and is a functional regulator of obesity-related insulin resistance (IR) that can be exploited therapeutically. Obesity induces a chronic phenotypic pro-inflammatory shift in bowel lamina propria immune cell populations. Reduction of the gut immune system, using beta7 integrin-deficient mice (Beta7null), decreases HFD-induced IR. Treatment of wild-type HFD C57BL/6 mice with the local gut anti-inflammatory, 5-aminosalicyclic acid (5-ASA), reverses bowel inflammation and improves metabolic parameters. These beneficial effects are dependent on adaptive and gut immunity and are associated with reduced gut permeability and endotoxemia, decreased visceral adipose tissue inflammation, and improved antigen-specific tolerance to luminal antigens. Thus, the mucosal immune system affects multiple pathways associated with systemic IR and represents a novel therapeutic target in this disease.

Original languageEnglish (US)
Pages (from-to)527-542
Number of pages16
JournalCell Metabolism
Volume21
Issue number4
DOIs
StatePublished - Apr 7 2015

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Insulin Resistance
Immune System
High Fat Diet
Anti-Inflammatory Agents
Obesity
Inflammation
Antigens
Endotoxemia
Intra-Abdominal Fat
Adaptive Immunity
Inbred C57BL Mouse
Permeability
Mucous Membrane
Acids
Population
Therapeutics

Cite this

Luck, H., Tsai, S., Chung, J., Clemente-Casares, X., Ghazarian, M., Revelo, X. S., ... Winer, D. A. (2015). Regulation of obesity-related insulin resistance with gut anti-inflammatory agents. Cell Metabolism, 21(4), 527-542. https://doi.org/10.1016/j.cmet.2015.03.001

Regulation of obesity-related insulin resistance with gut anti-inflammatory agents. / Luck, Helen; Tsai, Sue; Chung, Jason; Clemente-Casares, Xavier; Ghazarian, Magar; Revelo, Xavier S.; Lei, Helena; Luk, Cynthia T.; Shi, Sally Yu; Surendra, Anuradha; Copeland, Julia K.; Ahn, Jennifer; Prescott, David; Rasmussen, Brittany A.; Chng, Melissa Hui Yen; Engleman, Edgar G.; Girardin, Stephen E.; Lam, Tony K.T.; Croitoru, Kenneth; Dunn, Shannon; Philpott, Dana J.; Guttman, David S.; Woo, Minna; Winer, Shawn; Winer, Daniel A.

In: Cell Metabolism, Vol. 21, No. 4, 07.04.2015, p. 527-542.

Research output: Contribution to journalArticle

Luck, H, Tsai, S, Chung, J, Clemente-Casares, X, Ghazarian, M, Revelo, XS, Lei, H, Luk, CT, Shi, SY, Surendra, A, Copeland, JK, Ahn, J, Prescott, D, Rasmussen, BA, Chng, MHY, Engleman, EG, Girardin, SE, Lam, TKT, Croitoru, K, Dunn, S, Philpott, DJ, Guttman, DS, Woo, M, Winer, S & Winer, DA 2015, 'Regulation of obesity-related insulin resistance with gut anti-inflammatory agents', Cell Metabolism, vol. 21, no. 4, pp. 527-542. https://doi.org/10.1016/j.cmet.2015.03.001
Luck, Helen ; Tsai, Sue ; Chung, Jason ; Clemente-Casares, Xavier ; Ghazarian, Magar ; Revelo, Xavier S. ; Lei, Helena ; Luk, Cynthia T. ; Shi, Sally Yu ; Surendra, Anuradha ; Copeland, Julia K. ; Ahn, Jennifer ; Prescott, David ; Rasmussen, Brittany A. ; Chng, Melissa Hui Yen ; Engleman, Edgar G. ; Girardin, Stephen E. ; Lam, Tony K.T. ; Croitoru, Kenneth ; Dunn, Shannon ; Philpott, Dana J. ; Guttman, David S. ; Woo, Minna ; Winer, Shawn ; Winer, Daniel A. / Regulation of obesity-related insulin resistance with gut anti-inflammatory agents. In: Cell Metabolism. 2015 ; Vol. 21, No. 4. pp. 527-542.
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