ABSTRACT
The extension of life span driven by 40% caloric restriction (CR) in rodents causes trade-offs in growth, reproduction, and immune defense that make it difficult to identify therapeutically relevant CR-mimetic targets. We report that about 14% CR for 2 years in healthy humans improved thymopoiesis and was correlated with mobilization of intrathymic ectopic lipid. CR-induced transcriptional reprogramming in adipose tissue implicated pathways regulating mitochondrial bioenergetics, anti-inflammatory responses, and longevity. Expression of the gene Pla2g7 encoding platelet activating factor acetyl hydrolase (PLA2G7) is inhibited in humans undergoing CR. Deletion of Pla2g7 in mice showed decreased thymic lipoatrophy, protection against age-related inflammation, lowered NLRP3 inflammasome activation, and improved metabolic health. Therefore, the reduction of PLA2G7 may mediate the immunometabolic effects of CR and could potentially be harnessed to lower inflammation and extend the health span.
Subject(s)
1-Alkyl-2-acetylglycerophosphocholine Esterase/genetics , Adipose Tissue/metabolism , Caloric Restriction , Immune System/physiology , Inflammation , Thymus Gland/immunology , 1-Alkyl-2-acetylglycerophosphocholine Esterase/metabolism , Adult , Aging , Animals , Down-Regulation , Energy Metabolism , Female , Humans , Inflammasomes/metabolism , Longevity , Lymphopoiesis , Macrophages/immunology , Macrophages/metabolism , Male , Mice , Middle Aged , Mitochondria/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Thermogenesis , Thymus Gland/anatomy & histology , TranscriptomeABSTRACT
Fat embolism syndrome is a dire complication of long bone trauma. It is usually associated with neurological, hematological and respiratory involvement, the latter being the major cause of death. We present a case of severe fat embolism syndrome occurring 3 hours after a long bone injury, leading to permanent vegetative state and death without any respiratory signs. The diagnosis was confirmed by cytology of the bronchoalveolar lavage fluid. Clinical presentation of the puzzling fat embolism syndrome and diagnostic tests in suspected fat embolism syndrome are reviewed.