Decreased sarcoplasmic reticulum phospholipids in human skeletal muscle are associated with metabolic syndrome.

Metabolic syndrome affects more than one in three adults and is associated with increased risk of diabetes, cardiovascular disease, and all-cause mortality. Muscle insulin resistance is a major contributor to the development of the metabolic syndrome. Studies in mice have linked skeletal muscle sarcoplasmic reticulum (SR) phospholipid composition to sarcoplasmic/endoplasmic reticulum Ca2+-ATPase activity and insulin sensitivity. To determine if the presence of metabolic syndrome alters specific phosphatidylcholine (PC) and phosphatidylethanolamine (PE) species in human SR, we compared SR phospholipid composition in skeletal muscle from sedentary subjects with metabolic syndrome and sedentary control subjects without metabolic syndrome. Both total PC and total PE were significantly decreased in skeletal muscle SR of sedentary metabolic syndrome patients compared with sedentary controls, particularly in female participants, but there was no difference in the PC:PE ratio between groups. Total SR PC levels, but not total SR PE levels or PC:PE ratio, were significantly negatively correlated with BMI, waist circumference, total fat, visceral adipose tissue, triglycerides, fasting insulin, and homeostatic model assessment for insulin resistance. These findings are consistent with the existence of a relationship between skeletal muscle SR PC content and insulin resistance in humans.

MODY5 and Serous Ovarian Carcinoma in 17q12 Recurrent Deletion Syndrome.

Background/Objective: Maturity-onset diabetes of the young type 5 (MODY5) is caused by a hepatocyte nuclear factor 1ß (HNF1ß) gene mutation on chromosome 17q12. HNF1ß mutations have also been found in ovarian clear cell carcinoma, whereas ovarian non-clear cell carcinoma expresses this mutation rarely. 17q12 recurrent deletion syndrome features include MODY5, urogenital anomalies, and psychiatric and neurodevelopmental disorders. This is a report of a patient with 17q12 recurrent deletion syndrome with MODY5, uterine abnormalities, and low-grade serous ovarian cancer. Case Report: A 25-year-old woman with recently diagnosed stage IIIC low-grade serous ovarian carcinoma was evaluated at the endocrinology clinic for diabetes, which was diagnosed at the age of 12 years. C-peptide level was detectable and T1DM antibodies were negative. The mother had diabetes, partially septated uterus, and solitary kidney. Abdominal computed tomography showed pancreatic atrophy, ascites, omental and peritoneal nodularity, and calcifications. Laparoscopy revealed bicornuate uterus, 2 cervices, and vaginal septum. The patient underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy, lymph node dissection, and omentectomy. Chromosomal microarray analysis revealed a pathogenic ∼1.8 Mb loss of 17q12, denoted arr[hg19]17q12(34477479_36283807)x1. Discussion: 17q12deletion has been described as a susceptibility locus in some ovarian cancers. However, to our knowledge, predisposition to ovarian cancer as a feature of 17q12 recurrent deletion syndrome or MODY5 was not reported previously. Conclusion: The disease association reported suggests that medical providers should periodically evaluate for ovarian cancer, gut, and urogenital abnormalities in individuals with MODY5. Likewise, individuals with diabetes plus urogenital tract abnormalities or 17q12deletion in an ovarian tumor should undergo genetic testing for MODY5.

Enhanced fermentable sugar production in lignocellulosic biorefinery by exploring a novel corn stover and configuring high-solid pretreatment conditions.

This study aimed to produce enhanced fermentable sugars from a novel stover system through the bioprocessing of its soluble sugars and insoluble carbohydrates. The pretreatment conditions were optimized for this high sugar-containing stover (HSS) to control inhibitor formation and obtain enhanced fermentable sugar concentrations. The optimum temperature, acid loading, and reaction time for the pretreatment were 155 °C, 0.5%, and 30 min, respectively, providing up to 97.15% sugar yield and 76.51 g/L total sugars at 10% solid-load. Sugar concentration further increased to 126.9 g/L at 20% solid-load, generating 3.89 g/L acetate, 0.92 g/L 5-hydroxymethyl furfural, 0.82 g/L furfural, and 3.75 g/L total phenolics as inhibitors. To determine the effects of soluble sugars in HSS on fermentable sugar yield and inhibitor formation, sugar-removed HSS was further studied under the optimum conditions. Although prior removal of sugars exhibited a reduction in inhibitor generation, it also decreased total fermentable sugar production to 115.45 g/L.