Evidence mapPaperPMID 26394261Full record

ArticleApplied physiology, nutrition, and metabolism = Physiologie appliquee, nutrition et metabolisme2015

Combining metformin therapy with caloric restriction for the management of type 2 diabetes and nonalcoholic fatty liver disease in obese rats.

Melissa A Linden, Kristi T Lopez, Justin A Fletcher, E Matthew Morris, Grace M Meers, Sameer Siddique, M Harold Laughlin, James R Sowers, John P Thyfault, Jamal A Ibdah and 1 more

Open access · greenAbstract read
In one paragraph

Article in Applied physiology, nutrition, and metabolism = Physiologie appliquee, nutrition et metabolisme, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed
2.0field-weighted citation impact, top 14% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

26 citing papers in PubMed, 44 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Mechanism and regulation of mitophagy in liver diseases: a review.Frontiers in cell and developmental biology · 2025
    Review
  6. Review
  7. Article
  8. Article
  9. Article
  10. A dietary ketone ester mitigates histological outcomes of NAFLD and markers of fibrosis in high-fat diet fed mice.American journal of physiology. Gastrointestinal and liver physiology · 2021
    Article
  11. Review
  12. Article
  13. Review
  14. Review
  15. Review
  16. Review
  17. Article
  18. Article
  19. Article
  20. The Eeffect of Metformin Combined with Calcium-Vitamin DAdvanced pharmaceutical bulletin · 2018
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors at 2 institutions in 1 country.

Melissa A Lindena Research Service, Harry S. Truman Memorial Veterans' Hospital, Columbia, MO 65201, USA.
Kristi T Lopeza Research Service, Harry S. Truman Memorial Veterans' Hospital, Columbia, MO 65201, USA.
Justin A Fletchera Research Service, Harry S. Truman Memorial Veterans' Hospital, Columbia, MO 65201, USA.
E Matthew Morrisa Research Service, Harry S. Truman Memorial Veterans' Hospital, Columbia, MO 65201, USA.
Grace M Meersa Research Service, Harry S. Truman Memorial Veterans' Hospital, Columbia, MO 65201, USA.
Sameer Siddiquea Research Service, Harry S. Truman Memorial Veterans' Hospital, Columbia, MO 65201, USA.
M Harold Laughline Department of Biomedical Sciences, University of Missouri, Columbia, MO 65211, USA.
James R Sowersa Research Service, Harry S. Truman Memorial Veterans' Hospital, Columbia, MO 65201, USA.
John P Thyfaulta Research Service, Harry S. Truman Memorial Veterans' Hospital, Columbia, MO 65201, USA.
Jamal A Ibdaha Research Service, Harry S. Truman Memorial Veterans' Hospital, Columbia, MO 65201, USA.
R Scott Rectora Research Service, Harry S. Truman Memorial Veterans' Hospital, Columbia, MO 65201, USA.
University of Missouri · USHarry S. Truman Memorial Veterans' Hospital · US

Funding

TRAINING: MUSCLE BLOOD FLOW &CAPILLARY DYNAMICSR01HL036088 · UNIVERSITY OF MISSOURI-COLUMBIA · 1985 to 2005
$1.6M
Exercise &Health: Integration from Molecule to PatientT32AR048523 · UNIVERSITY OF MISSOURI-COLUMBIA · 2003 to 2005
$695k
ANG II OPPOSES INS MEDIATED VASORELAXATION &GLU UTILZAR01HL073101 · UNIVERSITY OF MISSOURI-COLUMBIA · 2004 to 2005
$586k
Cell Specific Mineralocorticoid Signaling, Insulin Resistance and Cardiovascular StiffnessI01BX001981 · VA · HARRY S. TRUMAN MEMORIAL VA HOSPITAL · PI Guido Lastra · 2021 to 2022
Sexual dimorphism, hepatic mitochondrial adaptations, and hepatic steatosisI01BX002567 · VA · KANSAS CITY VA MEDICAL CENTER · 2022 to 2025
BLRD VA I01 BX001981BLRD VA I01 BX002567BLRD VA IK2 BX001299NHLBI NIH HHS HL73101-07NHLBI NIH HHS R01 HL036088NHLBI NIH HHS R01HL036088NHLBI NIH HHS R01 HL073101NHLBI NIH HHS R01 HL107910NHLBI NIH HHS R01 HL107910-03NIAMS NIH HHS T32 AR048523NIAMS NIH HHS T32AR048523-07NIDDK NIH HHS DK088940NIDDK NIH HHS R01 DK088940
6 · The paper itself

Abstract

Weight loss is recommended for patients with nonalcoholic fatty liver disease (NAFLD), while metformin may lower liver enzymes in type 2 diabetics. Yet, the efficacy of the combination of weight loss and metformin in the treatment of NAFLD is unclear. We assessed the effects of metformin, caloric restriction, and their combination on NAFLD in diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats. Male OLETF rats (age 20 weeks; n = 6-8 per group) were fed ad libitum (AL), given metformin (300 mg·kg(-1)·day(-1); Met), calorically restricted (70% of AL; CR), or calorically restricted and given metformin (CR+Met) for 12 weeks. Met lowered adiposity compared with AL but not to the same magnitude as CR or CR+Met (p < 0.05). Although only CR improved fasting insulin and glucose, the combination of CR+Met was needed to improve post-challenge glucose tolerance. All treatments lowered hepatic triglycerides, but further improvements were observed in the CR groups (p < 0.05, Met vs. CR or CR+Met) and a further reduction in serum alanine aminotransferases was observed in CR+Met rats. CR lowered markers of hepatic de novo lipogenesis (fatty acid synthase, acetyl-CoA carboxylase (ACC), and stearoyl-CoA desaturase-1 (SCD-1)) and increased hepatic mitochondrial activity (palmitate oxidation and β-hydroxyacyl CoA dehydrogenase (β-HAD) activity). Changes were enhanced in the CR+Met group for ACC, SCD-1, β-HAD, and the mitophagy marker BNIP3. Met decreased total hepatic mTOR content and inhibited mTOR complex 1, which may have contributed to Met-induced reductions in de novo lipogenesis. These findings in the OLETF rat suggest that the combination of caloric restriction and metformin may provide a more optimal approach than either treatment alone in the management of type 2 diabetes and NAFLD.

Indexed as

Caloric RestrictionAnimalsBlotting, WesternDiabetes Mellitus, ExperimentalDiabetes Mellitus, Type 2Disease Models, AnimalHypoglycemic AgentsMetforminNon-alcoholic Fatty Liver DiseaseObesityRatsRats, Long-EvansHypoglycemic AgentsMetformincaloric restrictionde novo lipogenesisfonction mitochondrialehepatic steatosislipogenèse de novometforminmetforminemitochondrial functionnonalcoholic fatty liver diseaserestriction caloriquestéatose hépatiquestéatose hépatique non alcoolique

Identifiers

PMID26394261
PMCPMC4713237
OpenAlexW1859932611

What Socratic holds

Texttitle and abstract
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.