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

Elise Laperrousaz, Valentine S. Moullé, Raphaël G. Denis, Nadim Kassis, Chloé Berland, Benoit Colsch, Xavier Fioramonti, Erwann Philippe, Amélie Lacombe, Charlotte Vanacker, Noémie Butin, Kimberley D. Bruce, Hong Wang, Yongping Wang, Yuanqing Gao, Cristina Garcia-Caceres, Vincent Prévot, Matthias H. Tschöp, Robert H. Eckel, Hervé Le StunffSerge Luquet, Christophe Magnan, Céline Cruciani-Guglielmacci

Research output: Contribution to journalArticlepeer-review

24 Scopus citations


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.

Original languageEnglish
Pages (from-to)1314-1324
Number of pages11
Issue number7
StatePublished - 1 Jul 2017


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


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