ABSTRACT
Background: Sepsis can cause the nonthyroidal illness syndrome (NTIS), resulting in perturbed thyroid hormone (TH) signaling and reduced thyroxine (T4) levels. TH is a major regulator of muscle function, via its influence on mitochondria. This study aimed at evaluating the relationship between TH signaling, mitochondrial function, and the antioxidant defense system in the diaphragms of septic mice. Methods: Male C57Bl/6 mice were divided into two groups: cecal ligation and puncture (CLP) and sham. Twenty-four hours after surgery, plasma, diaphragms, and livers were collected. TH metabolism and responses were analyzed by measuring messenger RNA (mRNA) expression of Dio1 in the liver, and Thra, Thrb, Dio2, Slc16a10, and Slc16a2 (encodes MCT 10 and 8), in the diaphragm. T4 plasma levels were measured by radioimmunoassay. Damage to diaphragm mitochondria was assessed by electron microscopy and real-time polymerase chain reaction (qPCR), and function with oxygraphy. The diaphragm antioxidative defense system was examined by qPCR, analyzing superoxide dismutase (SOD) 1 (Sod1), mitochondrial superoxide dismutase (SOD 2; Sod2), extracellular superoxide dismutase (SOD 3; Sod3), glutathione peroxidase 1 (Gpx1), and catalase (Cat) expression. The effect of TH replacement was tested by treating the mice with T4 and triiodothyronine (T3) (CLP+TH) after surgery. Results: CLP mice presented reduced total plasma T4 concentrations, downregulated Dio1, and upregulated Il1b mRNA expression in the liver. CLP mice also displayed downregulated Thra, Thrb, Slc16a10, and Slc16a2 expression in the diaphragm, suggesting that TH signaling was compromised. The expression of Ppargc1a (encoding PGC1a) was downregulated, which correlated with the decrease in the number of total mitochondria, increase in the percentage of injured mitochondria, downregulation of respiratory chain complex 2 and 3 mRNA expression, and reduced maximal respiration. In addition, septic animals presented a three-fold increase in Ucp3 and G6pdh expression; downregulated Sod3, Gpx1, and Cat expression; and upregulated Sod2 expression, potentially due to elevated reactive oxygen species levels. The mitochondrial number and the percentage of injured mitochondrial were similar between sham and CLP+TH mice. Conclusions: Sepsis induced responses consistent with NTIS, resulted in mitochondrial damage and functional impairment, and modulated the expression of key antioxidant enzymes in the diaphragm. Thus, impaired diaphragm function during sepsis seems to involve altered local TH signaling, mitochondrial dysfunction, and oxidative stress defense.
Subject(s)
Diaphragm/metabolism , Mitochondria/metabolism , Sepsis/metabolism , Signal Transduction/physiology , Thyroid Hormones/metabolism , Animals , Disease Models, Animal , Gene Expression Regulation , Iodide Peroxidase/genetics , Iodide Peroxidase/metabolism , Liver/metabolism , Mice , Oxidative Stress/physiology , Reactive Oxygen Species/metabolismABSTRACT
BACKGROUND: Satiety decline is one of the factors that are involved in weight regain in the postoperative period of bariatric surgery. Nutrients such as long-chain n-3 polyunsaturated fatty acid and fibers could assist in food intake control by increasing satiety. Flaxseed is a source of these nutrients, and its consumption could help with possible glycemic control and increased satiety. The aim of this study was to evaluate the influence of whole flaxseed and defatted flaxseed on satiety, postprandial blood glucose, and leptin in post-bariatric women. METHODS: A single-blind crossover and randomized study was performed with 18 women in the late postoperative of Roux-en-Y gastric bypass (RYGBP). All women received three test meals containing whole flaxseed, defatted flaxseed, and placebo with 1 week of washout. Satiety was evaluated by a Visual Analog Scale during the fasting period; immediately after ingestion; and 60, 120, and 180 min after meals. RESULTS: There was no difference between test meals for the variables of hunger, satisfaction, fullness, and desire to eat. The basal and postprandial glucose and leptin levels did not differ between the test meals. The intake of defatted flaxseed and placebo muffins resulted in reduced postprandial blood glucose. Postprandial leptin was higher than the baseline (p = 0.02); however, only defatted flaxseed showed increased postprandial leptin levels (p = 0.044). CONCLUSIONS: Whole flaxseed and defatted flaxseed did not promote satiety in women in the late postoperative of RYGBP. However, the test meals with a lower fat content increased the serum leptin levels.
