Cited by 488Endoplasmic Reticulum Stress and DiseaseAdipokines, Inflammation, and Metabolic DiseasesBariatric Surgery and Outcomes

Endoplasmic reticulum stress is reduced in tissues of obese subjects after weight loss

Open access
Gregor, Margaret F., Yang, Ling, Fabbrini, Elisa, Mohammed, B. Selma, Eagon, J. Christopher, Hotamisligil, Gökhan S., Klein, Samuel·2009·Diabetes

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/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.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.2337/db08-1220

Cites

29 of 29 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Substantial weight loss in patients after bariatric surgery is associated with both improvements in insulin sensitivity and reduction in markers of endoplasmic-reticulum stress.

    “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]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Cited by

Sorted by citations

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
Published
2009-03-01
Volume
58
Issue
3
Pages
693-700
ISSN
  • 0012-1797 (ISSN-L)
  • 1939-327X
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
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 › Epidemiology › 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

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review