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LCoRL Regulates Growth and Metabolism.

Steven C Wyler1, Surbhi Gahlot1, Lara Bideyan1

  • 1Center for Hypothalamic Research, Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX 75390, USA.

Endocrinology
|October 28, 2024
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Summary
This summary is machine-generated.

Ligand-dependent corepressor-like (LCoRL) regulates body weight and glucose homeostasis. LCoRL knockout mice exhibit improved metabolic health, reduced food intake, and protection against high-fat diets, validating GWAS findings.

Keywords:
Lcorladipositybody weightexerciseglucose homeostasis

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Area of Science:

  • Metabolic regulation
  • Genetics
  • Physiology

Background:

  • Genome-wide association studies (GWAS) link genes to metabolic traits, but causality remains unclear.
  • Ligand-dependent corepressor-like (LCoRL) is associated with body size and glucose homeostasis in humans and livestock.
  • Functional analysis of LCoRL's role in metabolic regulation is lacking.

Purpose of the Study:

  • To investigate the functional role of LCoRL in metabolic homeostasis.
  • To characterize the metabolic traits of Lcorl knockout mice.
  • To elucidate the mechanisms underlying LCoRL's metabolic regulation.

Main Methods:

  • Generation and characterization of Lcorl knockout mice (Lcorl-/-).
  • Assessment of body weight, food intake, glucose tolerance, and insulin sensitivity.
  • Measurement of circulating IGF-1 levels and gene expression analysis in the liver.
  • Evaluation of response to high-fat diet and exercise stress test.

Main Results:

  • Lcorl-/- mice exhibit reduced birth weight but normalize by adulthood, remaining leaner with decreased food intake.
  • Improved glucose tolerance and insulin sensitivity were observed in Lcorl-/- mice.
  • Reduced circulating IGF-1 levels were linked to stunted growth.
  • Liver gene expression related to GH signaling, glucose, and lipid metabolism was altered.
  • Lcorl-/- mice showed protection against high-fat diet and reduced exercise capacity.

Conclusions:

  • LCoRL is a critical regulator of body weight and glucose homeostasis.
  • Lcorl deficiency confers protection against metabolic challenges.
  • These findings validate GWAS associations and highlight LCoRL as a potential therapeutic target for metabolic disorders.