Olfactomedin 2 deficiency protects against diet-induced obesity

Olfactomedin 2 (OLFM2; also known as noelin 2) is a pleiotropic protein that plays a major role in olfaction and Olfm2 null mice exhibit reduced olfactory sensitivity, as well as abnormal motor coordination and anxiety-related behavior. Here, we investigated the possible metabolic role of OLFM2. Olf...

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Published in:Metabolism, clinical and experimental clinical and experimental, 2022-04, Vol.129, p.155122-155122, Article 155122
Main Authors: González-García, Ismael, Freire-Agulleiro, Óscar, Nakaya, Naoki, Ortega, Francisco J., Garrido-Gil, Pablo, Liñares-Pose, Laura, Fernø, Johan, Labandeira-Garcia, José Luis, Diéguez, Carlos, Sultana, Afia, Tomarev, Stanislav I., Fernández-Real, José Manuel, López, Miguel
Format: Article
Language:English
Subjects:
Adipose Tissue, Brown - metabolism
Adipose Tissue, White - metabolism
Animals
Brown adipose tissue
Browning
Diet, High-Fat - adverse effects
Energy Metabolism - genetics
Extracellular Matrix Proteins
Glycoproteins
Lateral hypothalamic area
Mice
Mice, Inbred C57BL
Mice, Knockout
Obesity
Obesity - metabolism
Olfactomedin 2
Thermogenesis
Thermogenesis - genetics
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Summary:Olfactomedin 2 (OLFM2; also known as noelin 2) is a pleiotropic protein that plays a major role in olfaction and Olfm2 null mice exhibit reduced olfactory sensitivity, as well as abnormal motor coordination and anxiety-related behavior. Here, we investigated the possible metabolic role of OLFM2. Olfm2 null mice were metabolically phenotyped. Virogenetic modulation of central OLFM2 was also performed. Our data showed that, the global lack of OLFM2 in mice promoted anorexia and increased energy expenditure due to elevated brown adipose tissue (BAT) thermogenesis and browning of white adipose tissue (WAT). This phenotype led to resistance to high fat diet (HFD)-induced obesity. Notably, virogenetic overexpression of Olfm2 in the lateral hypothalamic area (LHA) induced weight gain associated with decreased BAT thermogenesis. Overall, this evidence first identifies central OLFM2 as a new molecular actor in the regulation of whole-body energy homeostasis. •Olfaction has emerged as an important regulator of metabolism.•Olfactomedin 2 (OLFM2) plays a major role in olfaction.•OLFM2 deficiency decreases feeding and increases energy expenditure.•OLMF2 deficiency protects against diet-induced obesity.•Overexpression of OLFM2 in the LHA promotes weight gain.
ISSN:0026-0495
1532-8600
DOI:10.1016/j.metabol.2021.155122