Lipoprotein lipase in hypothalamus is a key regulator of body weight gain and glucose homeostasis in mice
Diabetologia. 2017-04-29; 60(7): 1314-1324
DOI: 10.1007/s00125-017-4282-7
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1. Diabetologia. 2017 Jul;60(7):1314-1324. doi: 10.1007/s00125-017-4282-7. Epub
2017 Apr 29.
Lipoprotein lipase in hypothalamus is a key regulator of body weight gain and
glucose homeostasis in mice.
Laperrousaz E(1), Moullé VS(1), Denis RG(1), Kassis N(1), Berland C(1)(2)(3),
Colsch B(4), Fioramonti X(5), Philippe E(1), Lacombe A(1), Vanacker C(6), Butin
N(4), Bruce KD(7), Wang H(7), Wang Y(7), Gao Y(2)(3), Garcia-Caceres C(2)(3),
Prévot V(5), Tschöp MH(2)(3)(8), Eckel RH(7), Le Stunff H(1), Luquet S(1),
Magnan C(9), Cruciani-Guglielmacci C(10).
Author information:
(1)Unité de Biologie Fonctionnelle et Adaptative, Sorbonne Paris Cité, CNRS UMR
8251, Université Paris Diderot, Bâtiment Buffon, P. O. box 7126, 4, rue
Marie-Andrée Lagroua Weill-Halle, 75205, Paris Cedex 13, France.
(2)Institute for Diabetes and Obesity, Helmholtz Diabetes Center at Helmholtz
Zentrum, Munich, Germany.
(3)German Center for Diabetes Research (DZD), München-Neuherberg, Germany.
(4)CEA-Centre d’Etude de Saclay, Laboratoire d’étude du Métabolisme des
Médicaments, Gif-sur-Yvette, France.
(5)Centre des Sciences du Goût et de l’Alimentation, Unité Mixte de Recherche
CNRS, INRA, Université de Bourgogne, Dijon, France.
(6)Development and Plasticity of the Neuroendocrine Brain, Neurobese
International Associated Laboratory, Jean-Pierre Aubert Research Center, Inserm
U1172, University of Lille, Lille, France.
(7)Division of Endocrinology, Metabolism, & Diabetes, Department of Medicine,
University of Colorado, Denver Anschutz Medical Campus, Aurora, CO, USA.
(8)Division of Metabolic Diseases, Technische Universität München, Munich,
Germany.
(9)Unité de Biologie Fonctionnelle et Adaptative, Sorbonne Paris Cité, CNRS UMR
8251, Université Paris Diderot, Bâtiment Buffon, P. O. box 7126, 4, rue
Marie-Andrée Lagroua Weill-Halle, 75205, Paris Cedex 13, France.
.
(10)Unité de Biologie Fonctionnelle et Adaptative, Sorbonne Paris Cité, CNRS UMR
8251, Université Paris Diderot, Bâtiment Buffon, P. O. box 7126, 4, rue
Marie-Andrée Lagroua Weill-Halle, 75205, Paris Cedex 13, France.
.
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