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Authors wish to express their gratitude to Drs. Carlota Largo and Victor Caz from the Hospital Universitario La Paz for the hormonal tests, to Mr. Javier Perez CSIC for professional drafting of the illustrations, to Mrs. Teresa Navarro CSIC for expert maintenance of the MRI instrumentation and to Mrs. Patricia Sanchez CSIC for proficient technical assistance with animal housing and handling. The Phenomaster and MRI instrumentations are Central CSIC Research Resources of the Institute of Biomedical Research "Alberto Sols''. This work was supported in part by Grants SAF-2008-01327, SAF2011-23622 and IPT-2012-1331-006000 to SC, Grant CTQ-2010-20960-C02-02 to PLL, Grants S-BIO-2006-0170 and S2010/BMD-2349 to S.C. and PLL. BL held a predoctoral fellowship from the Spanish Ministry of Science and Technology (BES 2009-027615).

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Lizarbe, BlancaAuthor

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November 4, 2021
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fDWI Evaluation of Hypothalamic Appetite Regulation Pathways in Mice Genetically Deficient in Leptin or Neuropeptide Y

Publicated to:NEUROCHEMICAL RESEARCH. 40 (12): 2628-2638 - 2015-12-01 40(12), DOI: 10.1007/s11064-015-1596-z

Authors: Lizarbe, Blanca; Lopez-Larrubia, Pilar; Cerdan, Sebastian;

Affiliations

Inst Invest Biomed Alberto Sols CSIC UAM, C Arturo Duperier 4, Madrid 28029, Spain - Author

Abstract

We evaluate the contribution of leptin-dependent anorexigenic pathways and neuropeptide Y (NPY)-dependent orexigenic pathways to the changes in hypothalamic water diffusion parameters observed in vivo by functional diffusion weighted MRI (fDWI). Mice genetically deficient in leptin (B6.V-Lep(ob)/J) or NPY (129S-Npy(tm1Rpa)/J) and the corresponding wild-type controls, were subjected to sequential isocaloric feeding, fasting and recovery regimes. Non-invasive fDWI measurements were performed under these conditions, and complemented with parallel determinations of food and water consumption, respiratory exchange ratio (RER), locomotor activity and endocrine profiles. Control mice showed significant increases in hypothalamic water diffusion parameters upon fasting, returning to normal values in the recovery period. Leptin deficient mice depicted permanently increased water diffusion parameters under all feeding conditions as compared to wild type controls, without important changes upon fasting or recovery. These results paralleled sustained increases in food and water intake, significantly augmented body weight, and decreased RER values or locomotor activity, thus configuring an obese phenotype. NPY-deficient mice showed significantly reduced increases (or even slight decreases) in the water diffusion parameters upon fasting as compared to wild type controls, paralleled by decreased food and water intake during the recovery period. In conclusion, leptin deficiency results in sustained orexigenic stimulation, leading to increased water diffusion parameters, while NPY deficiency lead to reduced orexigenic stimulation and water diffusion parameters. Diffusion changes are proposed to reflect net astrocytic volume changes induced by the balance between the orexigenic and anorexigenic firings of AgRP/NPY and POMC/CART neurons, respectively. Together, our results suggest that fDWI provides an adequate tool to investigate hypothalamic appetite disorders.

Keywords

global energy balancehypothalamusleptinnpyAnimalsAppetite regulationAstrocytesBalanceBody waterDiffusion magnetic resonance imagingDiffusion mriDrinkingEatingEnergy-metabolismFdwiFood-intakeGlobal energy balanceHormonesHuman brainHypothalamusLeptinMiceMice, inbred c57blMice, knockoutMotor activityMouse hypothalamusNervous-system controlNeural pathwaysNeuronal activationNeuropeptide yNpyObesityPulmonary gas exchange

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Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal NEUROCHEMICAL RESEARCH due to its progression and the good impact it has achieved in recent years, according to the agency Scopus (SJR), it has become a reference in its field. In the year of publication of the work, 2015, it was in position , thus managing to position itself as a Q1 (Primer Cuartil), in the category Medicine (Miscellaneous).

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: 1.72, 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 Aug 2025)

Specifically, and according to different indexing agencies, this work has accumulated citations as of 2025-08-04, the following number of citations:

  • WoS: 10
  • Scopus: 9
  • Europe PMC: 5
  • Google Scholar: 12

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 2025-08-04:

  • 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: 28 (PlumX).

Leadership analysis of institutional authors

This work has been carried out with international collaboration, specifically with researchers from: Switzerland.

There is a significant leadership presence as some of the institution’s authors appear as the first or last signer, detailed as follows: First Author (LIZARBE SERRA, BLANCA) .