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Essential Role of IGFIR in the Onset of Male Brown Fat Thermogenic Function: Regulation of Glucose Homeostasis by Differential Organ-Specific Insulin Sensitivity.

Publicated to:ENDOCRINOLOGY. 157 (4): 1495-511 - 2016-04-01 157(4), DOI: 10.1210/en.2015-1623

Authors: Viana-Huete V, Guillén C, García-Aguilar A, García G, Fernández S, Kahn CR, Benito M

Affiliations

), Complutense University-Madrid, Madrid 28040, Spain - Author
), Harvard Medical School, Boston, MA 02215 - Author
), Institute of Health Carlos III, Madrid 28029, Spain - Author
g - Author
Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02215 USA - Author
Inst Hlth Carlos III, Spanish Diabet & Metab Res Network, Madrid 28029, Spain - Author
k - Author
R - Author
Univ Complutense Madrid, Biol Fac Pharm, Dept Biochem & Mol Biol, E-28040 Madrid, Spain - Author
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Abstract

Brown fat is a thermogenic tissue that generates heat to maintain body temperature in cold environments and dissipate excess energy in response to overfeeding. We have addressed the role of the IGFIR in the brown fat development and function. Mice lacking IGFIR exhibited normal brown adipose tissue/body weight in knockout (KO) vs control mice. However, lack of IGFIR decreased uncoupling protein 1 expression in interscapular brown fat and beige cells in inguinal fat. More importantly, the lack of IGFIR resulted in an impaired cold acclimation. No differences in the total fat volume were found in the KO vs control mice. Epididymal fat showed larger adipocytes but with a lower number of adipocytes in KO vs control mice at age 12 months. In addition, KO mice showed a sustained moderate hyperinsulinemia and hypertriglyceridemia upon time and hepatic insulin insensitivity associated with lipid accumulation, with the outcome of a global insulin resistance. In addition, we found that the expression of uncoupling protein 3 in the skeletal muscle was decreased and its expression was increased in the heart in parallel with the expression of beta-2 adrenergic receptors. Upon nonobesogenic high-fat diet, we found a severe insulin resistance in the liver and in the skeletal muscle, but unchanged insulin sensitivity in the heart. In conclusion, our data suggest that IGFIR it is not an essential growth factor in the brown fat development in the presence of the IR and very high plasma levels of IGF-I, but it is indispensable for full brown fat functionality.

Keywords

BiodiversidadeBiotecnologíaCiências biológicas iCiências biológicas iiCiências biológicas iiiEducação físicaEndocrinologyEndocrinology & metabolismEngenharias iiFarmaciaGeneral medicineInterdisciplinarMedicina iMedicina iiMedicina veterinariaNutriçãoOdontologíaPsicologíaQuímicaSaúde coletivaZootecnia / recursos pesqueiros

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal ENDOCRINOLOGY due to its progression and the good impact it has achieved in recent years, according to the agency WoS (JCR), it has become a reference in its field. In the year of publication of the work, 2016, it was in position 29/138, thus managing to position itself as a Q1 (Primer Cuartil), in the category Endocrinology & Metabolism.

From a relative perspective, and based on the normalized impact indicator calculated from the Field Citation Ratio (FCR) of the Dimensions source, it yields a value of: 2.65, which indicates that, compared to works in the same discipline and in the same year of publication, it ranks as a work cited above average. (source consulted: Dimensions Jul 2025)

Specifically, and according to different indexing agencies, this work has accumulated citations as of 2025-07-01, the following number of citations:

  • WoS: 13
  • Scopus: 12
  • Europe PMC: 11

Impact and social visibility

From the perspective of influence or social adoption, and based on metrics associated with mentions and interactions provided by agencies specializing in calculating the so-called "Alternative or Social Metrics," we can highlight as of 2025-07-01:

  • The use of this contribution in bookmarks, code forks, additions to favorite lists for recurrent reading, as well as general views, indicates that someone is using the publication as a basis for their current work. This may be a notable indicator of future more formal and academic citations. This claim is supported by the result of the "Capture" indicator, which yields a total of: 25 (PlumX).

It is essential to present evidence supporting full alignment with institutional principles and guidelines on Open Science and the Conservation and Dissemination of Intellectual Heritage. A clear example of this is:

  • The work has been submitted to a journal whose editorial policy allows open Open Access publication.

Leadership analysis of institutional authors

This work has been carried out with international collaboration, specifically with researchers from: Germany; United States of America.