Endoplasmic Reticulum Stress Is Reduced in Tissues of Obese Subjects After Weight Loss

Margaret F Gregor; Ling Yang; Elisa Fabbrini; B. Selma Mohammed; J. Christopher Eagon; Gökhan S Hotamisligil; Samuel Klein

doi:10.2337/db08-1220

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Endoplasmic Reticulum Stress Is Reduced in Tissues of Obese Subjects After Weight Loss

Journal article

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Endoplasmic Reticulum Stress Is Reduced in Tissues of Obese Subjects After Weight Loss

Margaret F Gregor, Ling Yang, Elisa Fabbrini, B. Selma Mohammed, J. Christopher Eagon, Gökhan S Hotamisligil and Samuel Klein

Diabetes (New York, N.Y.), Vol.58(3), pp.693-700

03/2009

DOI: 10.2337/db08-1220

PMCID: PMC2646068

PMID: 19066313

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Abstract

OBJECTIVE— Obesity is associated with insulin resistance and type 2 diabetes, although the mechanisms linking these pathologies remain undetermined. Recent studies in rodent models revealed endoplasmic reticulum (ER) stress in adipose and liver tissues and demonstrated that ER stress could cause insulin resistance. Therefore, we tested whether these stress pathways were also present in obese human subjects and/or regulated by weight loss. RESEARCH DESIGN AND METHODS— Eleven obese men and women (BMI 51.3 ± 3.0 kg/m 2 ) were studied before and 1 year after gastric bypass (GBP) surgery. We examined systemic insulin sensitivity using hyperinsulinemic-euglycemic clamp studies before and after surgery and collected subcutaneous adipose and liver tissues to examine ER stress markers. RESULTS— Subjects lost 39 ± 9% body wt at 1 year after GBP surgery ( P < 0.001), which was associated with a marked improvement in hepatic, skeletal muscle, and adipose tissue insulin sensitivity. Markers of ER stress in adipose tissue significantly decreased with weight loss. Specifically, glucose-regulated protein 78 (Grp78) and spliced X-box binding protein-1 (sXBP-1) mRNA levels were reduced, as were phosphorylated elongation initiation factor 2α (eIF2α) and stress kinase c-Jun NH 2 -terminal kinase 1 (JNK1) (all P values <0.05). Liver sections from a subset of subjects showed intense staining for Grp78 and phosphorylated eIF2α before surgery, which was reduced in post-GBP sections. CONCLUSIONS— This study presents important evidence that ER stress pathways are present in selected tissues of obese humans and that these signals are regulated by marked weight loss and metabolic improvement. Hence, this suggests the possibility of a relationship between obesity-related ER stress and metabolic dysfunction in obese humans.

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Title: Subtitle: Endoplasmic Reticulum Stress Is Reduced in Tissues of Obese Subjects After Weight Loss
Creators: Margaret F Gregor - Department of Genetics and Complex Diseases, Harvard School of Public Health, Boston, Massachusetts
Ling Yang - Department of Genetics and Complex Diseases, Harvard School of Public Health, Boston, Massachusetts
Elisa Fabbrini - Center for Human Nutrition, Washington University School of Medicine, St. Louis, Missouri
B. Selma Mohammed - Center for Human Nutrition, Washington University School of Medicine, St. Louis, Missouri
J. Christopher Eagon - Center for Human Nutrition, Washington University School of Medicine, St. Louis, Missouri
Gökhan S Hotamisligil - Department of Genetics and Complex Diseases, Harvard School of Public Health, Boston, Massachusetts
Samuel Klein - Center for Human Nutrition, Washington University School of Medicine, St. Louis, Missouri
Resource Type: Journal article
Publication Details: Diabetes (New York, N.Y.), Vol.58(3), pp.693-700
DOI: 10.2337/db08-1220
PMID: 19066313
PMCID: PMC2646068
NLM abbreviation: Diabetes
ISSN: 0012-1797
eISSN: 1939-327X
Publisher: American Diabetes Association
Language: English
Date published: 03/2009
Academic Unit: Molecular Physiology and Biophysics; Anatomy and Cell Biology
Record Identifier: 9984025355702771

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