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Laperrousaz, E.* ; Moullé, V.S.* ; Denis, R.G.* ; Kassis, N.* ; Berland, C. ; Colsch, B.* ; Fioramonti, X.* ; Philippe, E.* ; Lacombe, A.* ; Vanacker, C.* ; Butin, N.* ; Bruce, K.D.* ; Wang, H.* ; Wang, Y.* ; Gao, Y. ; García-Cáceres, C. ; Prévot, V.* ; Tschöp, M.H. ; Eckel, R.H.* ; Le Stunff, H.* ; Luquet, S.* ; Magnan, C.* ; Cruciani-Guglielmacci, C.*

Lipoprotein lipase in hypothalamus is a key regulator of body weight gain and glucose homeostasis in mice.

Diabetologia 60, 1314-1324 (2017)
Forschungsdaten DOI PMC
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
Aims/hypothesis: Regulation of energy balance involves the participation of many factors, including nutrients, among which are circulating lipids, acting as peripheral signals informing the central nervous system of the energy status of the organism. It has been shown that neuronal lipoprotein lipase (LPL) participates in the control of energy balance by hydrolysing lipid particles enriched in triacylglycerols. Here, we tested the hypothesis that LPL in the mediobasal hypothalamus (MBH), a well-known nucleus implicated in the regulation of metabolic homeostasis, could also contribute to the regulation of body weight and glucose homeostasis. Methods: We injected an adeno-associated virus (AAV) expressing Cre–green fluorescent protein into the MBH of Lpl-floxed mice (and wild-type mice) to specifically decrease LPL activity in the MBH. In parallel, we injected an AAV overexpressing Lpl into the MBH of wild-type mice. We then studied energy homeostasis and hypothalamic ceramide content. Results: The partial deletion of Lpl in the MBH in mice led to an increase in body weight compared with controls (37.72 ± 0.7 g vs 28.46 ± 0.12, p < 0.001) associated with a decrease in locomotor activity. These mice developed hyperinsulinaemia and glucose intolerance. This phenotype also displayed reduced expression of Cers1 in the hypothalamus as well as decreased concentration of several C18 species of ceramides and a 3-fold decrease in total ceramide intensity. Conversely, overexpression of Lpl specifically in the MBH induced a decrease in body weight. Conclusions/interpretation: Our study shows that LPL in the MBH is an important regulator of body weight and glucose homeostasis.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Hypothalamus ; Insulin Resistance ; Lipoprotein Lipase ; Nutrient Utilisation ; Obesity ; Triacylglycerol
Sprache englisch
Veröffentlichungsjahr 2017
HGF-Berichtsjahr 2017
ISSN (print) / ISBN 0012-186X
e-ISSN 1432-0428
Zeitschrift Diabetologia
Quellenangaben Band: 60, Heft: 7, Seiten: 1314-1324 Artikelnummer: , Supplement: ,
Verlag Springer
Verlagsort Berlin ; Heidelberg [u.a.]
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Diabetes and Obesity (IDO)
POF Topic(s) 30201 - Metabolic Health
90000 - German Center for Diabetes Research
Forschungsfeld(er) Helmholtz Diabetes Center
PSP-Element(e) G-502200-001
G-501900-221
PubMed ID 28456865
DOI 10.1007/s00125-017-4282-7
Scopus ID 85018362547
Erfassungsdatum 2017-06-09
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