Effect of revascularization on lower extremity muscle function in combined type 2 diabetes and critical limb threatening ischemia.

Background: Critical limb-threatening ischemia (CLTI) and type 2 diabetes (T2D) frequently co-exist and often with less favorable outcome after revascularization. The objective was to evaluate the effects of revascularization on muscle function, perfusion and mitochondrial respiration in patients with combined CLTI and T2D.

Methods: A prospective translational observational study.

Pyruvate kinase M2 represses thermogenic gene expression in brown adipocytes.

Utilizing the thermogenic capacity of brown adipose tissue is a potential anti-obesity strategy; therefore, the mechanisms controlling expression of thermogenesis-related genes are of interest. Pyruvate kinase (PK) catalyzes the last step of glycolysis and exists as four isoenzymes: PK, liver, PK, red blood cell, PK, muscle (PKM1 and PKM2). PKM2 has both glycolytic and nuclear functions.

Design of Gadoteridol-Loaded Cationic Liposomal Adjuvant CAF01 for MRI of Lung Deposition of Intrapulmonary Administered Particles.

Designing effective and safe tuberculosis (TB) subunit vaccines for inhalation requires identification of appropriate antigens and adjuvants and definition of the specific areas to target in the lungs. Magnetic resonance imaging (MRI) enables high spatial resolution, but real-time anatomical and functional MRI of lungs is challenging. Here, we describe the design of a novel gadoteridol-loaded cationic adjuvant formulation 01 (CAF01) for MRI-guided vaccine delivery of the clinically tested TB subunit vaccine candidate H56/CAF01.

Elevated arterial lactate delays recovery of intracellular muscle pH after exercise.

Purpose: We evaluated muscle proton elimination following similar exercise in the same muscle group following two exercise modalities.

Methods: Seven rowers performed handgrip or rowing exercise for ~ 5 min. The intracellular response of the wrist flexor muscles was evaluated by P nuclear magnetic resonance spectroscopy, while arterial and venous forearm blood was collected.

Diabetes, myometrium, and mitochondria in pregnant women at term.

Aims: Poor myometrial contractility has been demonstrated in women at term with diabetes and decreased muscular mitochondrial content and/or function has been extensively implicated in the progression of type 2 diabetes. Alterations of the uterine mitochondrial phenotype in pregnant women with diabetes have yet to be investigated as a causal link to decreased myometrial contractility.

Methods: Observational study of 18 women with diabetes (type 2 and gestational) scheduled for an elective Caesarean section at term with matching controls.

Fetal over- and undernutrition differentially program thyroid axis adaptability in adult sheep.

Objective: We aimed to test, whether fetal under- or overnutrition differentially program the thyroid axis with lasting effects on energy metabolism, and if early-life postnatal overnutrition modulates implications of prenatal programming.

Design: Twin-pregnant sheep ( = 36) were either adequately (NORM), under- (LOW; 50% of NORM) or overnourished (HIGH; 150% of energy and 110% of protein requirements) in the last-trimester of gestation. From 3 days-of-age to 6 months-of-age, twin lambs received a conventional (CONV) or an obesogenic, high-carbohydrate high-fat (HCHF) diet.

Perturbations of NAD salvage systems impact mitochondrial function and energy homeostasis in mouse myoblasts and intact skeletal muscle.

Nicotinamide adenine dinucleotide (NAD) can be synthesized by nicotinamide phosphoribosyltransferase (NAMPT). We aimed to determine the role of NAMPT in maintaining NAD levels, mitochondrial function, and metabolic homeostasis in skeletal muscle cells. We generated stable Nampt knockdown (sh Nampt KD) C2C12 cells using a shRNA lentiviral approach.

Unchanged mitochondrial phenotype, but accumulation of lipids in the myometrium in obese pregnant women.

Key Points: Obesity during pregnancy and childbirth is associated with labour dystocia leading to instrumental or operative delivery, but the underlying pathophysiological mechanisms remain unclear and insufficient uterine contractility has been suggested. This study examined whether reduced myometrial mitochondrial capacity or quantity could contribute as a pathophysiological mechanism to labour dystocia. Data did not support reduced myometrial mitochondrial capacity or quantity in the myometrium at term in obese women, but a reduced myocyte density with increased triglyceride content was demonstrated, which could lead to poorer uterine contractility.

Restricting glycolysis impairs brown adipocyte glucose and oxygen consumption.

During thermogenic activation, brown adipocytes take up large amounts of glucose. In addition, cold stimulation leads to an upregulation of glycolytic enzymes. Here we have investigated the importance of glycolysis for brown adipocyte glucose consumption and thermogenesis.

Gestational Protein Restriction in Wistar Rats; Effect of Taurine Supplementation on Properties of Newborn Skeletal Muscle.

Taurine ameliorates changes occurring in newborn skeletal muscle as a result of gestational protein restriction in C57BL/6 mice, but taurine supplementation effects may be exaggerated in C57BL/6 mice due to their inherent excessive taurinuria.We examined if maternal taurine supplementation could ameliorate changes in gene expression levels, properties of mitochondria, myogenesis, and nutrient transport and sensing, in male newborn skeletal muscle caused by a maternal low protein (LP) diet in Wistar rats.LP diet resulted in an 11% non-significant decrease in birth weight, which was not rescued by taurine supplementation (LP-Tau).

Quantitative Gd-DOTA uptake from cerebrospinal fluid into rat brain using 3D VFA-SPGR at 9.4T.

Purpose: We propose a quantitative technique to assess solute uptake into the brain parenchyma based on dynamic contrast-enhanced MRI (DCE-MRI). With this approach, a small molecular weight paramagnetic contrast agent (Gd-DOTA) is infused in the cerebral spinal fluid (CSF) and whole brain gadolinium concentration maps are derived.

Methods: We implemented a 3D variable flip angle spoiled gradient echo (VFA-SPGR) longitudinal relaxation time (T1) technique, the accuracy of which was cross-validated by way of inversion recovery rapid acquisition with relaxation enhancement (IR-RARE) using phantoms.

Your mitochondria are what you eat: a high-fat or a high-sucrose diet eliminates metabolic flexibility in isolated mitochondria from rat skeletal muscle.

Extreme diets consisting of either high fat (HF) or high sucrose (HS) may lead to insulin resistance in skeletal muscle, often associated with mitochondrial dysfunction. However, it is not known if these diets alter normal interactions of pyruvate and fatty acid oxidation at the level of the mitochondria. Here, we report that rat muscle mitochondria does show the normal fat-carbohydrate interaction seen in vivo.

Mitochondrial dysfunction in calf muscles of patients with combined peripheral arterial disease and diabetes type 2.

Background: This study elucidates the effects on muscle mitochondrial function in patients suffering from combined peripheral arterial disease (PAD) and type 2 diabetes (T2D) and the relation to patient symptoms and treatment.

Methods: Near infrared spectroscopy (NIRS) calf muscle exercise tests were conducted on 40 subjects, 15 (PAD), 15 (PAD+T2D) and 10 healthy age matched controls (CTRL) recruited from the vascular outpatient clinic at Gentofte County Hospital, Denmark. Calf muscle biopsies (~80 mg, gastrocnemius and anterior tibial muscles) were sampled and mitochondrial function tested applying high resolution oxygraphy on isolated muscle fibers.

Acute disruption of glucagon secretion or action does not improve glucose tolerance in an insulin-deficient mouse model of diabetes.

Aims/hypothesis: Normal glucose metabolism depends on pancreatic secretion of insulin and glucagon. The bihormonal hypothesis states that while lack of insulin leads to glucose underutilisation, glucagon excess is the principal factor in diabetic glucose overproduction. A recent study reported that streptozotocin-treated glucagon receptor knockout mice have normal glucose tolerance.

Inflammatory and Metabolic Alterations of Kager's Fat Pad in Chronic Achilles Tendinopathy.

Background: Achilles tendinopathy is a painful inflammatory condition characterized by swelling, stiffness and reduced function of the Achilles tendon. Kager's fat pad is an adipose tissue located in the area anterior to the Achilles tendon. Observations reveal a close physical interplay between Kager's fat pad and its surrounding structures during movement of the ankle, suggesting that Kager's fat pad may stabilize and protect the mechanical function of the ankle joint.

Global gene expression profiling of brown to white adipose tissue transformation in sheep reveals novel transcriptional components linked to adipose remodeling.

Background: Large mammals are capable of thermoregulation shortly after birth due to the presence of brown adipose tissue (BAT). The majority of BAT disappears after birth and is replaced by white adipose tissue (WAT).

Results: We analyzed the postnatal transformation of adipose in sheep with a time course study of the perirenal adipose depot.

A near infrared spectroscopy-based test of calf muscle function in patients with peripheral arterial disease.

Background The study aims to test a new, simple, and reliable apparatus and procedure for the diagnostics and treatment evaluation of peripheral arterial disease (PAD). The test apparatus involves near infrared spectroscopy (NIRS) of a main part of the lower leg muscles during isometric flexion and extension of the ankle joint performed with the foot strapped in a specially designed pedal ergometer. Design To evaluate the reproducibility of the new test compared with an existing testing method of treadmill walking.

One-year high fat diet affects muscle-but not brain mitochondria.

It is well known that few weeks of high fat (HF) diet may induce metabolic disturbances and mitochondrial dysfunction in skeletal muscle. However, little is known about the effects of long-term HF exposure and effects on brain mitochondria are unknown. Wistar rats were fed either chow (13E% fat) or HF diet (60E% fat) for 1 year.

Aberrant expression of miR-218 and miR-204 in human mesial temporal lobe epilepsy and hippocampal sclerosis-convergence on axonal guidance.

Objective: Mesial temporal lobe epilepsy (MTLE) is one of the most common types of the intractable epilepsies and is most often associated with hippocampal sclerosis (HS), which is characterized by pronounced loss of hippocampal pyramidal neurons. microRNAs (miRNAs) have been shown to be dysregulated in epilepsy and neurodegenerative diseases, and we hypothesized that miRNAs could be involved in the pathogenesis of MTLE and HS.

Methods: miRNA expression was quantified in hippocampal specimens from human patients using miRNA microarray and quantitative real-time polymerase chain reaction RT-PCR, and by RNA-seq on fetal brain specimens from domestic pigs.

Effect of high-fat diet on rat myometrium during pregnancy-isolated myometrial mitochondria are not affected.

Laboring women with elevated body mass index (BMI) have an increased risk of inefficient uterine labor contractions, and despite the significance of mitochondria in the production of energy to drive uterine contractions, mitochondrial function in the myometrium with reference to the BMI has not been explored. The objective of this study was to determine whether obesity prior to and during gestation affects oxidative capacity and/or morphology of mitochondria in the myometrium at term in an animal model. Rat dams were fed for 47 days prior to impregnation and during gestation with either (1) a regular chow diet, (2) a low-fat high-carbohydrate diet, or (3) a high-fat low-carbohydrate diet (n = 10 in each group).

Acute and perinatal programming effects of a fat-rich diet on rat muscle mitochondrial function and hepatic lipid accumulation.

Objective: Maternal high-fat intake during pregnancy may have long-term consequences in the offspring. Since this might relate to the capacity of mitochondrial metabolic adaptation and hepatic lipid metabolism, we investigated how maternal high-fat intake affected mitochondrial function and hepatic steatosis in the offspring.

Design: Sprague-Dawley rats were fed a high-fat (20% w/w) or a control diet (chow, C) from 10 days before pregnancy and throughout lactation.