Adipocyte-specific deletion of lamin A/C largely models human familial partial lipodystrophy type 2

CAS Corsa, CM Walsh, DP Bagchi, MC Foss Freitas… - Diabetes, 2021 - Am Diabetes Assoc
CAS Corsa, CM Walsh, DP Bagchi, MC Foss Freitas, Z Li, J Hardij, K Granger, H Mori
Diabetes, 2021Am Diabetes Assoc
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 …
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 (LmnaADKO). Although LmnaADKO 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. LmnaADKO 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 LmnaADKO 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. LmnaADKO mice faithfully reproduce many characteristics of FPLD2 and thus provide a unique animal model to investigate mechanisms underlying Lmna-dependent loss of adipose tissues.
Am Diabetes Assoc