The endogenous cannabinoid system affects energy balance via central orexigenic drive and peripheral lipogenesis
Authors: Cristina Cervino
Alexander Yassouridis
Uberto Pagotto
Federica Tomassoni
Astrid C E Linthorst
Enzo Nisoli
Sylvia Ortmann
Giovanni Marsicano
Christa Thöne-Reineke
Günter K Stalla
Daniela Cota
Dorothee Auer
Mirjam Schubert
Matthias Tschöp
Cornelia Flachskamm
Renato Pasquali
Yvonne Grübler
Beat Lutz
Journal: Journal of Clinical Investigation (2003)
Discipline: CLINICAL MEDICINE
Keywords: cannabinoid receptor type 1; endocannabinoids; food intake regulation; hypophagia; leanness
Affiliations: Clinical Neuroendocrinology Group, Max-Planck-Institute of Psychiatry, Munich, Germany.

Abstract:  The cannabinoid receptor type 1 (CB1) and its endogenous ligands, the endocannabinoids, are involved in the regulation of food intake. Here we show that the lack of CB1 in mice with a disrupted CB1 gene causes hypophagia and leanness. As compared with WT (CB1+/+) littermates, mice lacking CB1 (CB1-/-) exhibited reduced spontaneous caloric intake and, as a consequence of reduced total fat mass, decreased body weight. In young CB1-/- mice, the lean phenotype is predominantly caused by decreased caloric intake, whereas in adult CB1-/- mice, metabolic factors appear to contribute to the lean phenotype. No significant differences between genotypes were detected regarding locomotor activity, body temperature, or energy expenditure. Hypothalamic CB1 mRNA was found to be coexpressed with neuropeptides known to modulate food intake, such as corticotropin-releasing hormone (CRH), cocaine-amphetamine-regulated transcript (CART), melanin-concentrating hormone (MCH), and preproorexin, indicating a possible role for endocannabinoid receptors within central networks governing appetite. CB1-/- mice showed significantly increased CRH mRNA levels in the paraventricular nucleus and reduced CART mRNA levels in the dorsomedial and lateral hypothalamic areas. CB1 was also detected in epidydimal mouse adipocytes, and CB1-specific activation enhanced lipogenesis in primary adipocyte cultures. Our results indicate that the cannabinoid system is an essential endogenous regulator of energy homeostasis via central orexigenic as well as peripheral lipogenic mechanisms and might therefore represent a promising target to treat diseases characterized by impaired energy balance. 

Retracted: No

PubPeer comments:
 This paper belongs to a set of over 400 papers (as per February 2020) that share very similar Western blots with tadpole-like shaped bands, the same background pattern, and striking similarities in title structures, paper layout, bar graph design, and - in a subset - flow cytometry panels. Despite these similarities, these papers are authored by researchers from different departments and institutes, with almost no overlap in authors. The list of these papers is available here: https: docs.google.com spreadsheets d 1KXqTAyl4j-jVorFPMD2XRpr76LcIKJ0CVyIvRj0exYQ edit?usp=sharing A more detailed description of this set of papers, suspected to all be generated by a common source, a paper mill , can be found here: * https: forbetterscience.com 2020 01 24 the-full-service-paper-mill-and-its-chinese-customers (January 2020) * https: scienceintegritydigest.com 2020 02 21 the-tadpole-paper-mill (February 2020) The same paper mill has been described in these papers: * Jana Christopher - Systematic fabrication of scientific images revealed - FEBS Letters (2018) - https: febs.onlinelibrary.wiley.com doi full 10.1002 1873-3468.13201 * Jennifer A Byrne and Jana Christopher - Digital magic, or the dark arts of the 21st centuryu2014how can journals and peer reviewers detect manuscripts and publications from paper mills? - FEBS Letters (2020) - https: febs.onlinelibrary.wiley.com doi full 10.1002 1873-3468.13747 , 
 Recently retracted: https: www.cellphysiolbiochem.com Articles 000420 PDF 000420.pdf Kudos to the Editor for perseverance. ----------------------- The article has been retracted by the current and former Publishers and the Editor. After the publication of this article, concerns were raised about the integrity of some of the data presented. The authors responded to our request for the raw data however additional concerns were identified in the raw data. The authors were unresponsive to follow-up correspondence within the given timeframe. The matter was raised to the corresponding author s institution who did not respond to our request for an investigation. Given the serious nature of the concerns raised, the article has been retracted by the current and former publishers. The authors have not responded to our correspondence regarding this retraction despite multiple attempts of contact. ,