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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.

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. Christophe.magnan@univ-paris-diderot.fr.
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. cruciani@univ-paris-diderot.fr.

Abstract

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.

KEYWORDS:

Hypothalamus; Insulin resistance; Lipoprotein lipase; Nutrient utilisation; Obesity; Triacylglycerol

PMID:
28456865
DOI:
10.1007/s00125-017-4282-7
[Indexed for MEDLINE]

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