Lipid Profile In Patients With Primary Immunodeficiency

Caetano, Mauricio S.; Silva, R.; Ferreira, Caroline; Sarni, Roseli Saccardo; Carvalho, Beatriz

doi:10.1016/j.jaci.2010.12.269

Cited by 2 publications

(1 citation statement)

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“…Several genetic defects in the NF-κB signaling pathway are associated with PIDs [58–62], including recently described patients with loss-of-function mutations in NIK [10, 11]. Patients with PIDs have been observed to have growth defects, mainly in children [63, 64]. Risk for infection have also been linked to factors including body mass index and adipose deposition due to the immunomodulatory effects of the tissue, but less is understood of the metabolic dynamics in patients with PIDs [65, 66].…”

Section: Discussionmentioning

confidence: 99%

NF-κB-Inducing Kinase Maintains Mitochondrial Efficiency and Systemic Metabolic Homeostasis

Pflug

Lee

Sitcheran

2021

Preprint

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Obesity is a predominant risk factor for metabolic syndrome, which refers to a cluster of disorders that include diabetes, cardiovascular disease and fatty liver disease. Obesity and overnutrition are associated with aberrant immune and inflammatory responses resulting in increased local fat deposition, insulin resistance and systemic metabolic dysregulation. Here we show NF-κB-inducing kinase (NIK), a critical regulator of immunity and inflammation has local and systemic effects on metabolic processes. We demonstrate that NIK has NF-κB-independent and -dependent roles on adipose development and function. Independently of noncanonical NF-κB, NIK deficiency regulates mitochondrial spare respiratory capacity (SRC) and proton leak but establishes higher basal oxygen consumption and glycolytic capacity in preadipocytes and ex vivo adipose tissue. In addition, we demonstrate NIK promotes adipogenesis through its role in activation of the noncanonical NF-κB pathway. Strikingly, when challenged with a high fat diet, NIK deficient mice are protected against diet-induced obesity and insulin insensitivity. Overall, mice lacking NIK exhibit decreased overall fat mass and increased energy expenditure. Our results establish that, through its influences on adipose development, metabolic homeostasis and rewiring, NIK is a driver of pathologies associated with metabolic dysfunction.

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