triolein and Hypoxia

Obstructive sleep apnea (OSA) induces intermittent hypoxia (IH) during sleep and is associated with elevated triglycerides (TG). We previously demonstrated that mice exposed to chronic IH develop elevated TG. We now hypothesize that a single exposure to acute hypoxia also increases TG due to the stimulation of free fatty acid (FFA) mobilization from white adipose tissue (WAT), resulting in increased hepatic TG synthesis and secretion. Male C57BL6/J mice were exposed to FiO(2) = 0.21, 0.17, 0.14, 0.10, or 0.07 for 6 h followed by assessment of plasma and liver TG, glucose, FFA, ketones, glycerol, and catecholamines. Hypoxia dose-dependently increased plasma TG, with levels peaking at FiO(2) = 0.07. Hepatic TG levels also increased with hypoxia, peaking at FiO(2) = 0.10. Plasma catecholamines also increased inversely with FiO(2). Plasma ketones, glycerol, and FFA levels were more variable, with different degrees of hypoxia inducing WAT lipolysis and ketosis. FiO(2) = 0.10 exposure stimulated WAT lipolysis but decreased the rate of hepatic TG secretion. This degree of hypoxia rapidly and reversibly delayed TG clearance while decreasing [(3)H]triolein-labeled Intralipid uptake in brown adipose tissue and WAT. Hypoxia decreased adipose tissue lipoprotein lipase (LPL) activity in brown adipose tissue and WAT. In addition, hypoxia decreased the transcription of LPL, peroxisome proliferator-activated receptor-γ, and fatty acid transporter CD36. We conclude that acute hypoxia increases plasma TG due to decreased tissue uptake, not increased hepatic TG secretion.

Topics: Acute Disease; Animals; Dietary Fats; Emulsions; Fat Emulsions, Intravenous; Hypertriglyceridemia; Hypoxia; Lipolysis; Male; Metabolic Clearance Rate; Mice; Mice, Inbred C57BL; Oxygen; Phospholipids; Soybean Oil; Triglycerides; Triolein; Up-Regulation

Glyceryl trioleate has been injected into greyhounds as a model of the fat embolism syndrome. Pulmonary vascular pressures, systemic arterial pressure and cardiac output were determined at regular intervals over an 8-hour period. It has been shown that glyceryl tioleate causes an increased pulmonary vascular resistance and a fall in cardiac output. These effects are mediated partly by a direct mechanical block of pulmonary vessels and partly through a thrombogenic property of the injected fat. The relevance of these findings to the clinical situation is discussed and a sequence of events for the fat embolism syndrome is proposed.

Topics: Animals; Blood Pressure; Cardiac Output; Dogs; Embolism, Fat; Hypoxia; Lung; Myocardium; Pulmonary Artery; Time Factors; Triolein; Vascular Resistance

The acute effects of a triolein infusion in dogs were secondary to the mechanical effects of this neutral fat which was distributed in the pulmonary and systemic vascular tree of all organs without inflammatory change. Hypoxia developed immediately and became progressively worse as the infusion was continued. Pulmonary hypertension developed during the fat infusion without pneumonia, congestive heart failure or pulmonary edema. There was a slow leak of 14C triolein into the systemic circulation rather than a rapid shower, and this radioactive fat was recirculated between the pulmonary and systemic vasculature. Seventy-six per cent of the 14C triolein was retained in the lungs. Terminally, the dogs had a respiratory arrest without cardiac decompensation, cardiac arrest or pulmonary edema; cerebral fat embolism in addition to severe hypoxia appears to be the cause.

Topics: Acute Disease; Animals; Blood; Blood Circulation; Blood Pressure; Carbon Dioxide; Carbon Radioisotopes; Dogs; Embolism, Fat; Hydrogen-Ion Concentration; Hypertension, Pulmonary; Hypoxia; Liver; Lung; Pulmonary Circulation; Respiration; Triolein

Topics: Animals; Biopsy; Blood Coagulation Tests; Bone and Bones; Collagen; Disease Models, Animal; Disseminated Intravascular Coagulation; Dogs; Embolism, Fat; Exudates and Transudates; Fibrin; Fractures, Bone; Hindlimb; Hypoxia; Leukocytes; Lung; Microscopy; Microscopy, Electron; Muscles; Musculoskeletal System; Pulmonary Edema; Pulmonary Embolism; Triolein

Topics: Animals; Autopsy; Dogs; Embolism, Fat; Fatty Acids, Nonesterified; Fractures, Bone; Humans; Hypoxia; Injections, Intravenous; Intracranial Embolism and Thrombosis; Iodine Isotopes; Lethal Dose 50; Lung; Oleic Acids; Oxygen; Pulmonary Embolism; Rabbits; Triolein

Topics: Animals; Embolism, Fat; Hypoxia; Injections, Intra-Arterial; Injections, Intravenous; Intracranial Embolism and Thrombosis; Iodine Isotopes; Lung; Oxygen Inhalation Therapy; Pneumothorax; Pulmonary Embolism; Rabbits; Triolein

Topics: Animals; Brain Chemistry; Embolism, Fat; Hypoxia; Intracranial Embolism and Thrombosis; Iodine Isotopes; Kidney; Liver; Lung; Methods; Oxygen; Pneumothorax; Pulmonary Circulation; Pulmonary Embolism; Rabbits; Radioisotopes; Respiration; Rubidium; Triolein

Topics: Animals; Brain Chemistry; Embolism, Fat; Fatty Acids, Nonesterified; Female; Hypoxia; Iodine Isotopes; Lipase; Liver; Lung; Male; Rabbits; Respiration; Triolein