| Title |
Liver-specific reconstitution of CEACAM1 reverses the metabolic abnormalities caused by its global deletion in male mice
|
|---|---|
| Published in |
Diabetologia, September 2017
|
| DOI | 10.1007/s00125-017-4432-y |
| Pubmed ID | |
| Authors |
Lucia Russo, Harrison T. Muturi, Hilda E. Ghadieh, Simona S. Ghanem, Thomas A. Bowman, Hye Lim Noh, Sezin Dagdeviren, Godwin Y. Dogbey, Jason K. Kim, Garrett Heinrich, Sonia M. Najjar |
| Abstract |
The carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) promotes insulin clearance. Mice with global null mutation (Cc1 (-/-)) or with liver-specific inactivation (L-SACC1) of Cc1 (also known as Ceacam1) gene display hyperinsulinaemia resulting from impaired insulin clearance, insulin resistance, steatohepatitis and obesity. Because increased lipolysis contributes to the metabolic phenotype caused by transgenic inactivation of CEACAM1 in the liver, we aimed to further investigate the primary role of hepatic CEACAM1-dependent insulin clearance in insulin and lipid homeostasis. To this end, we examined whether transgenic reconstitution of CEACAM1 in the liver of global Cc1 (-/-) mutant mice reverses their abnormal metabolic phenotype. Insulin response was assessed by hyperinsulinaemic-euglycaemic clamp analysis and energy balance was analysed by indirect calorimetry. Mice were overnight-fasted and refed for 7 h to assess fatty acid synthase activity in the liver and the hypothalamus in response to insulin release during refeeding. Liver-based rescuing of CEACAM1 restored insulin clearance, plasma insulin level, insulin sensitivity and steatohepatitis caused by global deletion of Cc1. It also reversed the gain in body weight and total fat mass observed with Cc1 deletion, in parallel to normalising energy balance. Mechanistically, reversal of hyperphagia appeared to result from reducing fatty acid synthase activity and restoring insulin signalling in the hypothalamus. Despite the potential confounding effects of deleting Cc1 from extrahepatic tissues, liver-based rescuing of CEACAM1 resulted in full normalisation of the metabolic phenotype, underscoring the key role that CEACAM1-dependent hepatic insulin clearance pathways play in regulating systemic insulin sensitivity, lipid homeostasis and energy balance. |
X Demographics
The data shown below were collected from the profiles of 11 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 2 | 18% |
| Denmark | 2 | 18% |
| France | 2 | 18% |
| Serbia | 1 | 9% |
| Brazil | 1 | 9% |
| United Kingdom | 1 | 9% |
| Spain | 1 | 9% |
| Unknown | 1 | 9% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 5 | 45% |
| Practitioners (doctors, other healthcare professionals) | 4 | 36% |
| Scientists | 2 | 18% |
Mendeley readers
The data shown below were compiled from readership statistics for 21 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 21 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 5 | 24% |
| Student > Ph. D. Student | 4 | 19% |
| Student > Bachelor | 2 | 10% |
| Student > Master | 2 | 10% |
| Unspecified | 1 | 5% |
| Other | 1 | 5% |
| Unknown | 6 | 29% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 6 | 29% |
| Biochemistry, Genetics and Molecular Biology | 2 | 10% |
| Agricultural and Biological Sciences | 2 | 10% |
| Sports and Recreations | 1 | 5% |
| Unspecified | 1 | 5% |
| Other | 0 | 0% |
| Unknown | 9 | 43% |
Attention Score in Context
This research output has an Altmetric Attention Score of 6. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 28 February 2021.
All research outputs
#5,692,544
of 23,322,966 outputs
Outputs from Diabetologia
#2,441
of 5,122 outputs
Outputs of similar age
#88,171
of 317,016 outputs
Outputs of similar age from Diabetologia
#85
of 100 outputs
Altmetric has tracked 23,322,966 research outputs across all sources so far. Compared to these this one has done well and is in the 75th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
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