Impaired Suppression of Plasma Lipid Extraction and its Partitioning Away from Muscle by Insulin in Humans with Obesity.

Context: Humans with obesity and insulin resistance exhibit lipid accumulation in skeletal muscle, but the underlying biological mechanisms responsible for the accumulation of lipid in the muscle of these individuals remain unknown.

Objective: We investigated how plasma insulin modulates the extraction of circulating triglycerides (TGs) and non-esterified fatty acids (NEFAs) from ingested and endogenous origin in the muscle of lean, insulin-sensitive humans (Lean-IS) and contrasted these responses to those in humans with obesity and insulin resistance (Obese-IR).

Methods: The studies were performed in a postprandial state associated with steady-state plasma TG concentrations.

Impaired Suppression of Plasma Lipid Extraction and its Partitioning Away from Muscle by Insulin in Humans with Obesity.

Context: Humans with obesity and insulin resistance exhibit lipid accumulation in skeletal muscle, but the underlying biological mechanisms responsible for the accumulation of lipid in the muscle of these individuals remain unknown.

Objective: We investigated how plasma insulin modulates the extraction of circulating triglycerides (TGs) and non-esterified fatty acids (NEFAs) from ingested and endogenous origin in the muscle of lean, insulin-sensitive humans (Lean-IS) and contrasted these responses to those in humans with obesity and insulin resistance (Obese-IR).

Methods: The studies were performed in a postprandial state associated with steady-state plasma TG concentrations.

Lack of Increase in Muscle Mitochondrial Protein Synthesis During the Course of Aerobic Exercise and Its Recovery in the Fasting State Irrespective of Obesity.

Acute aerobic exercise induces skeletal muscle mitochondrial gene expression, which in turn can increase muscle mitochondrial protein synthesis. In this regard, the peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α), is a master regulator of mitochondrial biogenesis, and thus mitochondrial protein synthesis. However, PGC-1α expression is impaired in muscle of humans with obesity in response to acute aerobic exercise.

Mitochondrial ATP synthase β-subunit production rate and ATP synthase specific activity are reduced in skeletal muscle of humans with obesity.

New Findings: What is the central question of this study? Humans with obesity have lower ATP synthesis in muscle along with lower content of the β-subunit of the ATP synthase (β-F1-ATPase), the catalytic component of the ATP synthase. Does lower synthesis rate of β-F1-ATPase in muscle contribute to these responses in humans with obesity? What is the main finding and its importance? Humans with obesity have a lower synthesis rate of β-F -ATPase and ATP synthase specific activity in muscle. These findings indicate that reduced production of subunits forming the ATP synthase in muscle may contribute to impaired generation of ATP in obesity.

Lower Fasted-State but Greater Increase in Muscle Protein Synthesis in Response to Elevated Plasma Amino Acids in Obesity.

Objective: Obesity alters protein metabolism in skeletal muscle, but consistent evidence is lacking. This study compared muscle protein synthesis in adults with obesity and in lean controls in the fasted state and during an amino acid infusion.

Methods: Ten subjects with obesity (age: 36 ± 3 years; BMI: 34 ± 1 kg/m ) and ten controls (age: 35 ± 3 years; BMI: 23 ± 1 kg/m ) received an infusion of L-[2,3,3,4,5,5,5,6,6,6- H ]leucine (0.

Prolonged Exposure of Primary Human Muscle Cells to Plasma Fatty Acids Associated with Obese Phenotype Induces Persistent Suppression of Muscle Mitochondrial ATP Synthase β Subunit.

Our previous studies show reduced abundance of the β-subunit of mitochondrial H+-ATP synthase (β-F1-ATPase) in skeletal muscle of obese individuals. The β-F1-ATPase forms the catalytic core of the ATP synthase, and it is critical for ATP production in muscle. The mechanism(s) impairing β-F1-ATPase metabolism in obesity, however, are not completely understood.

Insulin does not stimulate muscle protein synthesis during increased plasma branched-chain amino acids alone but still decreases whole body proteolysis in humans.

Insulin stimulates muscle protein synthesis when the levels of total amino acids, or at least the essential amino acids, are at or above their postabsorptive concentrations. Among the essential amino acids, branched-chain amino acids (BCAA) have the primary role in stimulating muscle protein synthesis and are commonly sought alone to stimulate muscle protein synthesis in humans. Fourteen healthy young subjects were studied before and after insulin infusion to examine whether insulin stimulates muscle protein synthesis in relation to the availability of BCAA alone.

CaMKIIα knockdown decreases anxiety in the open field and low serotonin-induced upregulation of GluA1 in the basolateral amygdala.

Hyperactivation of the amygdala is implicated in anxiety and mood disorders, but the precise underlying mechanisms are unclear. We previously reported that depletion of serotonin (5-hydroxytryptamine, 5-HT) in the basolateral nucleus of the amygdala (BLA) using the serotonergic neurotoxin 5,7-dihydroxytryptamine (5,7-DHT) potentiated learned fear and increased glutamate receptor (Glu) expression in BLA. Here we investigated the hypothesis that CaMKII facilitates anxiety-like behavior and increased Glu/AMPA receptor subunit A1 (GluA1) expression following depletion of 5-HT in the BLA.

A new method to measure muscle protein synthesis in humans by endogenously introduced d9-leucine and using blood for precursor enrichment determination.

Enrichment from the easily accessible blood amino acid pool is commonly used as precursor enrichment to calculate rates of muscle protein fractional synthesis in relevant human studies in lieu of the less accessible muscle fluid amino acid pool. However, the accuracy of this approach depends largely on the extent to which there is low discrepancy in free amino acid enrichment between blood and muscle. Steady-state gradient (i.

Chiral amine enantiomeric excess determination using self-assembled octahedral Fe(II)-imine complexes.

A receptor assembly composed of iron(II) triflate and pyridine-2,6-dicarbaldehyde was used to determine the enantiomeric excess (ee) of alpha-chiral primary amines using circular dichroism spectroscopy. The alpha chiral amines condense with the dialdehyde to form a diimine, which forms a 2:1 octahedral complex with iron(II). The ee values of unknown concentrations of alpha-chiral amines were determined by constructing calibration curves for each amine and then measuring the ellipticity at 600 nm.

Importance of CRF receptor-mediated mechanisms of the bed nucleus of the stria terminalis in the processing of anxiety and pain.

Corticotropin-releasing factor (CRF)-mediated mechanisms in the bed nucleus of the stria terminalis (BNST) have a pivotal role in stress-induced anxiety and hyperalgesia. Although CRF is known to activate two receptor subtypes, CRF1 and CRF2, attempts to delineate the specific role of each subtype in modulating anxiety and nociception have been inconsistent. Here we test the hypothesis that CRF1 and CRF2 receptor activation in the anteriolateral BNST (BNSTAL) facilitates divergent mechanisms modulating comorbid anxiety and hyperalgesia.

Age-associated remodeling of the intestinal epithelial barrier.

Disorders of the gastrointestinal tract are common in the elderly people; however, the precise trait(s) of aging that contribute to the vulnerability of the gastrointestinal tract are poorly understood. Recent evidence suggests that patients with gastrointestinal disorders have increased intestinal permeability. Here, we address the hypothesis that disruption of the intestinal barrier is associated with aging.

Indoleamine 2,3-dioxygenase activity contributes to local immune suppression in the skin expressing human papillomavirus oncoprotein e7.

Chronic infection of anogenital epithelium with human papillomavirus (HPV) promotes development of cancer. Many pathogens evoke immunosuppressive mechanisms to enable persistent infection. We have previously shown that grafted skin expressing HPV16 E7 oncoprotein from a keratin-14 promoter (K14E7) is not rejected by a syngeneic, immunocompetent host.

5-HT Receptor Activation Normalizes Exaggerated Fear Behavior in -Chlorophenylalanine (PCPA)-Treated Rats.

Deficits in serotonin (5-hydroxytryptamine, 5-HT) neurotransmission are implicated in abnormal emotional behaviors such as aggression, anxiety, and depression. However, the specific 5-HT receptor mechanisms involved are not well understood. The role of 5-HT receptors in fear potentiated startle, (FPS) was examined in rats chronically treated with -chlorophenylalanine (PCPA) to reduce brain 5-HT.

Altered expression of glucocorticoid receptor and corticotropin-releasing factor in the central amygdala in response to elevated corticosterone.

The amygdala is not only a critical site for the generation of anxiety and fear, but is involved in the affective processing of sensory information including nociception. Previously, we demonstrated that the stress hormone corticosterone (CORT) localized to the central nucleus of the amygdala (CeA) induces anxiety-like behavior and increases the sensitivity to visceral or somatic stimuli in rats. Here we test the hypothesis that exposure of the CeA to elevated CORT alters the expression of key receptors and ion channels that are implicated in anxiety and pain processing.

The role of the anteriolateral bed nucleus of the stria terminalis in stress-induced nociception.

Activation of the central amygdala (CeA) by corticosterone (CORT) induces somatic and colonic hypersensitivity through corticotrophin-releasing factor (CRF)-dependent mechanisms. However, the importance of the bed nucleus of the stria terminalis (BNST), part of the extended amygdala, on nociception remains unexplored. In the present study, we test the hypothesis that stimulation of the CeA by CORT induces somatic and colonic hypersensitivity through activation of the anteriolateral BNST (BNST(AL)).

In situ assembly of octahedral Fe(II) complexes for the enantiomeric excess determination of chiral amines using circular dichroism spectroscopy.

A method for discriminating between α-chiral primary amine enantiomers is reported. The method utilizes circular dichroism (CD) spectroscopy and a sensing ensemble composed of 2-formyl-3-hydroxypyridine (4) and Fe(II)(TfO)(2). Aldehyde 4 reacts rapidly with chiral amines to form chiral imines, which complex Fe(II) to form a series of diastereomeric octahedral complexes that are CD-active in both the UV and visible regions of the spectrum.

Lateralized amygdala activation: importance in the regulation of anxiety and pain behavior.

Background: The amygdala is involved in the emotional responses to fear including anxiety and heightened pain reporting. In a rodent model, bilateral activation of the central amygdala (CeA) with corticosterone (CORT) produces anxiety-like behavior, somatic allodynia and visceral hypersensitivity. Although hemisphere-specific processing differences between the left and right amygdala have been reported, it remains unclear whether the right or left CeA is involved in the production of anxiety-like behavior, and abnormal somatic and visceral perception.

P-chlorophenylalanine increases glutamate receptor 1 transcription in rat amygdala.

The amygdala is a key limbic structure strongly implicated in both epilepsy and anxiety disorders. Epilepsy-like mechanisms involve an increased glutamatergic activity, whereas disturbances in serotonin [5-hydroxytryptamine (5-HT)] systems are associated with anxiety-like behavior. Previous studies suggest that low 5-HT increases amygdala excitability, but the molecular mechanisms are not well characterized.