Syk Is Recruited to Stress Granules and Promotes Their Clearance through Autophagy.

Syk is a cytoplasmic kinase that serves multiple functions within the immune system to couple receptors for antigens and antigen-antibody complexes to adaptive and innate immune responses. Recent studies have identified additional roles for the kinase in cancer cells, where its expression can either promote or suppress tumor cell growth, depending on the context. Proteomic analyses of Syk-binding proteins identified several interacting partners also found to be recruited to stress granules. We show here that the treatment of cells with inducers of stress granule formation leads to the recruitment of Syk to these protein-RNA complexes. This recruitment requires the phosphorylation of Syk on tyrosine and results in the phosphorylation of proteins at or near the stress granule. Grb7 is identified as a Syk-binding protein involved in the recruitment of Syk to the stress granule. This recruitment promotes the formation of autophagosomes and the clearance of stress granules from the cell once the stress is relieved, enhancing the ability of cells to survive the stress stimulus.

Serum autotaxin is independently associated with hepatic steatosis in women with severe obesity.

OBJECTIVE: Autotaxin (ATX) is an adipocyte-derived lysophospholipase that generates the lipid signaling molecule lysophosphatidic acid (LPA). The aim of this study was to determine the relationship between serum ATX and nonalcoholic fatty liver disease (NAFLD) in females with obesity. METHODS: 101 nondiabetic women with obesity (age: 31.5-55.8 years; BMI: 35.0-64.5 kg/m2) were classified as having NAFLD (36.3%) or not having NAFLD (63.7%) based on the degree of hepatic steatosis on abdominal CT. Subjects were characterized for metabolic phenotype including measures of energy, glucose, and lipid homeostasis. Fasting serum adipokines and inflammatory markers were determined by ELISA. Linear regression analysis was used to determine features independently associated with NAFLD. RESULTS: Subjects with and without NAFLD differed in several key features of metabolic phenotype including BMI, waist circumference, fasting glucose and insulin, HOMA-IR, VLDL, triglycerides, and ALT. Serum adipokines, including ATX and leptin, were higher in subjects with NAFLD. Serum ATX was significantly correlated with alkaline phosphatase, fasting glucose, fasting insulin, and HOMA-IR. Linear regression analysis revealed that serum triglycerides and log-transformed ATX were independently associated with hepatic steatosis. CONCLUSIONS: Serum ATX may be a potential pathogenic factor and/or biomarker for NAFLD in nondiabetic women with obesity.

Serum Autotaxin/ENPP2 correlates with insulin resistance in older humans with obesity.

OBJECTIVE: Autotaxin (ATX) is an adipocyte-derived lysophospholipase D that generates the lipid signaling molecule lysophosphatidic acid (LPA). The ATX/LPA pathway in adipose tissue has recently been implicated in obesity and insulin resistance in animal models, but the role of circulating ATX in humans remains unclear. The aim of the present study was to determine the relationship between serum ATX and insulin resistance. METHODS: Older (60-75 years), nondiabetic human participants with overweight or obesity (BMI 25-37 kg m(-2) ) were characterized for metabolic phenotype including measures of energy, glucose, and lipid homeostasis. The relationship between serum ATX and metabolic parameters was then determined using correlative and predictive statistics. RESULTS: Serum ATX was higher in females than in males. After controlling for sex, serum ATX correlated with multiple measures of adiposity and glucose homeostasis/insulin action. Serum ATX and BMI also independently predicted glucose infusion rate during a hyperinsulinemic euglycemic clamp and homeostatic model assessment of insulin resistance after controlling for sex and medication use. CONCLUSIONS: Serum ATX correlates with and predicts measures of glucose homeostasis and insulin sensitivity in older humans, suggesting that it may be a potential pathogenic factor and/or diagnostic/therapeutic target for insulin resistance in this population.