ena-STUDY-INSTITUTO DE AGROQUIMICA Y TECNOLOGIA DE ALIMENTOS-24-07-2019-23:27:01:459-920
NOD1 activity attenuates obesity in mice fed a high fat diet
The contribution of the nucleotide-binding oligomerization domain protein NOD1 to obesity has been investigated in mice fed a high fat diet. Absence of NOD1 accelerates obesity under these conditions resulting in an 11% increase in body weight after two weeks and 29% after 6 weeks when compared with the corresponding wild type counterparts. The obesity was due to an increase in the mass of white and inguinal adipose tissues. Analysis of the resting energy expenditure showed an impaired function in NOD1-deficient animals, compatible with an alteration in thyroid hormone homeostasis. The levels of free thyroidal T3 and T4 decrease in NOD1-deficient mice under a standard diet when compared to the wild type animals. However, free thyroidal T4 increases in NOD1-deficient mice fed a high fat diet. The brown adipose tissue and the liver also showed a diminished content of T3 when compared to the NOD1 WT mice, the deiodinases changing accordingly. In agreement to this, the expression levels of UCP1 in brown adipose tissue were significantly lower in NOD1-deficient mice than in the wild type animals under high fat diet, contributing to the observed adiposity in NOD1-deficient mice. Feeding a high fat diet resulted in an alteration of the proinflammatory profile of these animals, with an increase in the infiltration of inflammatory cells in the liver and the white adipose tissue, and an elevation of the circulating levels of TNF-a, mainly produced by the liver. NOD1-deficient mice also show alterations in the gut microbiota, which seem to increase the vulnerability of their ecosystem to the HFD challenge and could contribute to worsen the immune-metabolic phenotype of obese mice. Together, the data are compatible with a protective function of NOD1 against low-grade inflammation and obesity under nutritional conditions enriched with lipidic components. Moreover, one of the key regulators of this early obesity onset is a dysregulation in the metabolism and release of thyroid hormones, which represents a new player in the metabolic actions controlled by NOD1.
The contribution of the nucleotide-binding oligomerization domain protein NOD1 to obesity has been investigated in mice fed a high fat diet. Absence of NOD1 accelerates obesity under these conditions resulting in an 11% increase in body weight after two weeks and 29% after 6 weeks when compared with the corresponding wild type counterparts. The obesity was due to an increase in the mass of white and inguinal adipose tissues. Analysis of the resting energy expenditure showed an impaired function in NOD1-deficient animals, compatible with an alteration in thyroid hormone homeostasis. The levels of free thyroidal T3 and T4 decrease in NOD1-deficient mice under a standard diet when compared to the wild type animals. However, free thyroidal T4 increases in NOD1-deficient mice fed a high fat diet. The brown adipose tissue and the liver also showed a diminished content of T3 when compared to the NOD1 WT mice, the deiodinases changing accordingly. In agreement to this, the expression levels of UCP1 in brown adipose tissue were significantly lower in NOD1-deficient mice than in the wild type animals under high fat diet, contributing to the observed adiposity in NOD1-deficient mice. Feeding a high fat diet resulted in an alteration of the proinflammatory profile of these animals, with an increase in the infiltration of inflammatory cells in the liver and the white adipose tissue, and an elevation of the circulating levels of TNF-a, mainly produced by the liver. NOD1-deficient mice also show alterations in the gut microbiota, which seem to increase the vulnerability of their ecosystem to the HFD challenge and could contribute to worsen the immune-metabolic phenotype of obese mice. Together, the data are compatible with a protective function of NOD1 against low-grade inflammation and obesity under nutritional conditions enriched with lipidic components. Moreover, one of the key regulators of this early obesity onset is a dysregulation in the metabolism and release of thyroid hormones, which represents a new player in the metabolic actions controlled by NOD1.