Tissue-specific disruption of Kbtbd2 uncovers adipocyte-intrinsic and -extrinsic features of the teeny lipodystrophy syndrome.
Proc Natl Acad Sci U S A
; 117(21): 11829-11835, 2020 05 26.
Article
em En
| MEDLINE
| ID: mdl-32381739
ABSTRACT
Loss of KBTBD2 in all tissues causes the teeny phenotype, characterized by insulin resistance with late failure of insulin production, severe hyperglycemia/diabetes, lipodystrophy, hepatosteatosis, and growth retardation. KBTBD2 maintains insulin sensitivity in adipocytes by restricting the abundance of p85α. However, the possible physiological contribution or contributions of KBTBD2 have not yet been examined in other tissues. Here we show that mice with an adipocyte-specific knockout of Kbtbd2 accumulate p85α in white and brown adipose tissues, causing insulin resistance, moderate rather than severe hyperglycemia, sustained hyperinsulinemia without late failure of insulin production, and lipodystrophy leading to ectopic lipid accumulation in the liver. Adipocyte-extrinsic insulin resistance was observed in liver and muscle. None of these abnormalities were observed in liver- or muscle-specific Kbtbd2 knockout mice. Mice with Kbtbd2 knockout in adipocytes, liver, and muscle all showed normal growth, suggesting that KBTBD2 may be necessary to ensure IGF1 signaling in other tissues, notably bone. While much of the teeny phenotype results from loss of KBTBD2 in adipocytes, some features are adipocyte-extrinsic.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Resistência à Insulina
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Adipócitos
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Complexos Ubiquitina-Proteína Ligase
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Lipodistrofia
Limite:
Animals
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article