Adipocyte-Specific Deletion of Lamin A/C Largely Models Human Familial Partial Lipodystrophy Type 2

© 2021 by the American Diabetes Association..

Mechanisms by which autosomal recessive mutations in Lmna cause familial partial lipodystrophy type 2 (FPLD2) are poorly understood. To investigate the function of lamin A/C in adipose tissue, we created mice with an adipocyte-specific loss of Lmna (Lmna ADKO). Although Lmna ADKO mice develop and maintain adipose tissues in early postnatal life, they show a striking and progressive loss of white and brown adipose tissues as they approach sexual maturity. Lmna ADKO mice exhibit surprisingly mild metabolic dysfunction on a chow diet, but on a high-fat diet they share many characteristics of FPLD2 including hyperglycemia, hepatic steatosis, hyperinsulinemia, and almost undetectable circulating adiponectin and leptin. Whereas Lmna ADKO mice have reduced regulated and constitutive bone marrow adipose tissue with a concomitant increase in cortical bone, FPLD2 patients have reduced bone mass and bone mineral density compared with controls. In cell culture models of Lmna deficiency, mesenchymal precursors undergo adipogenesis without impairment, whereas fully differentiated adipocytes have increased lipolytic responses to adrenergic stimuli. Lmna ADKO mice faithfully reproduce many characteristics of FPLD2 and thus provide a unique animal model to investigate mechanisms underlying Lmna-dependent loss of adipose tissues.

Medienart:

E-Artikel

Erscheinungsjahr:

2021

Erschienen:

2021

Enthalten in:

Zur Gesamtaufnahme - volume:70

Enthalten in:

Diabetes - 70(2021), 9 vom: 04. Sept., Seite 1970-1984

Sprache:

Englisch

Beteiligte Personen:

Corsa, Callie A S [VerfasserIn]
Walsh, Carolyn M [VerfasserIn]
Bagchi, Devika P [VerfasserIn]
Foss Freitas, Maria C [VerfasserIn]
Li, Ziru [VerfasserIn]
Hardij, Julie [VerfasserIn]
Granger, Katrina [VerfasserIn]
Mori, Hiroyuki [VerfasserIn]
Schill, Rebecca L [VerfasserIn]
Lewis, Kenneth T [VerfasserIn]
Maung, Jessica N [VerfasserIn]
Azaria, Ruth D [VerfasserIn]
Rothberg, Amy E [VerfasserIn]
Oral, Elif A [VerfasserIn]
MacDougald, Ormond A [VerfasserIn]

Links:

Volltext

Themen:

Journal Article
Lamin Type A
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Anmerkungen:

Date Completed 08.11.2021

Date Revised 02.09.2022

published: Print-Electronic

figshare: 10.2337/figshare.14691045

Citation Status MEDLINE

doi:

10.2337/db20-1001

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM326369643