The DOI matches its Crossref record; 28 of the 29 references it cites were found in a registry or an index.
Endoplasmic Reticulum Stress Is Reduced in Tissues of Obese Subjects After Weight Loss
Open accessAbstract
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/m2) 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 2alpha (eIF2alpha) and stress kinase c-Jun NH2-terminal kinase 1 (JNK1) (all P values <0.05). Liver sections from a subset of subjects showed intense staining for Grp78 and phosphorylated eIF2alpha 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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“Substantial weight loss in patients after bariatric surgery has also been associated with both improvements in insulin sensitivity and reduction in markers of endoplasmic-reticulum stress.132”
From Lipid-induced insulin resistance: unravelling the mechanism (2010) · cites this paper as [132]
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Cites
Inflammation and metabolic disorders
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“In the past decade, it was recognized and established that chronic inflammatory and stress responses are a central feature of obesity, insulin resistance, and type 2 diabetes and contribute to the metabolic imbalance (4).”
BackgroundSignal integration in the endoplasmic reticulum unfolded protein response
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“The UPR is initiated by three ER transmembrane sensors (namely PERK (PKR-like ER-regulated kinase), IRE-1 (inositolrequiring enzyme-1), and ATF-6 (activating transcription factor-6) which activate an adaptive response that results in cessation of protein translation and transcriptional increase in proteinfolding chape…”
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BackgroundEndoplasmic Reticulum Stress Links Obesity, Insulin Action, and Type 2 Diabetes
Özcan, U., Cao, Q., Yilmaz, E., Lee, A.-H., Iwakoshi, N. N., Özdelen, E., Tuncman, G., Görgün, C., Glimcher, L. H., & Hotamisligil, G. S. (2004) · Science · doi:10.1126/science.1103160 · Cited by 3,844 · cited 3×
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Mohamed-Ali, V. (1997) · Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.82.12.4196 · Cited by 717
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Mechanisms of Insulin Action and Insulin Resistance
Petersen, M. C., & Shulman, G. I. (2018) · Physiological Reviews · doi:10.1152/physrev.00063.2017 · Cited by 3,028
Endoplasmic reticulum stress and the inflammatory basis of metabolic disease
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“Finally, we showed that when obese patients undergo marked weight loss due to gastric by-pass surgery, there is a decrease in ER stress markers in liver and adipose tissue (Gregor et al., 2009).”
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Metadata
- Authors
- Gregor, M. F., Yang, L., Fabbrini, E., Mohammed, B. S., Eagon, J. C., Hotamisligil, G. S., & Klein, S.
- Affiliations
- Harvard University (US)
- Washington University in St. Louis (US)
- Department of Genetics and Complex Diseases, Harvard School of Public Health, Boston, Massachusetts
- Corresponding author
- Klein, Samuel
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 2009-03-01
- Volume
- 58
- Issue
- 3
- Pages
- 693-700
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- PMC
- PMC2646068
- OpenAlex
- W2122631753
- Cited by
- 488
- References
- 29
- Citations by year
- 2026: 7 · 2025: 13 · 2024: 16 · 2023: 22 · 2022: 22 · 2021: 22 · 2020: 25 · 2019: 19 · 2018: 28 · 2017: 31 · 2016: 32 · 2015: 47 · 2014: 38 · 2013: 42 · 2012: 43
- FWCI
- 11.82
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc-nd
- Locations
- Diabetes (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Digital Commons@Becker (Washington University School of Medicine) (submittedVersion)
- Funders
- American Diabetes Association
- National Institutes of Health (5t32es007155-24, UL1TR000448)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK52539, DK37948, DK56341, R01DK037948, R01DK052539, P30DK056341, P30DK040561)
- National Institute of Environmental Health Sciences (T32-ES007155, T32 ES007155-24)
- National Center for Research Resources (UL1RR024992)
- National Center for Advancing Translational Sciences
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Endoplasmic Reticulum Stress and Disease
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Surgery › Bariatric Surgery and Outcomes
- Keywords
- endoplasmic reticulum stress, obesity, weight loss, gastric bypass, insulin resistance, type 2 diabetes, adipose tissue, liver, skeletal muscle, GRP78, eIF2α, JNK1, insulin sensitivity
- MeSH terms
- Endoplasmic Reticulum Chaperone BiP, Adipose Tissue, Endoplasmic Reticulum, Female, Follow-Up Studies, Humans, Hyperinsulinism, Insulin Resistance, Liver, Male, Middle Aged, Obesity, Stress, Physiological, Glucose Clamp Technique, Gastric Bypass, Muscle, Skeletal
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