Forkhead box O3 plays a role in skeletal muscle atrophy through expression of E3 ubiquitin ligases MuRF-1 and atrogin-1 in Cushings syndrome
Cushing’s syndrome is caused by overproduction of the adrenocorticotropic hormone (ACTH), which stimulates the adrenal grand to make cortisol. Skeletal muscle wasting occurs in pathophysiological response to Cushing’s syndrome. The forkhead box (FOX) protein family has been implicated as a key regulator of muscle loss under conditions such as diabetes and sepsis. However, the mechanistic role of the FOXO family in ACTH-induced muscle atrophy is not understood. We hypothesized that FOXO3a plays a role in muscle atrophy through expression of the E3 ubiquitin ligases, muscle RING finger protein-1 (MuRF-1), and atr...
Source: AJP: Endocrinology and Metabolism - June 1, 2017 Category: Endocrinology Authors: Kang, S.-H., Lee, H.-A., Kim, M., Lee, E., Sohn, U. D., Kim, I. Tags: Research Article Source Type: research
Comprehensive functional screening of miRNAs involved in fat cell insulin sensitivity among women
In conclusion, miR-143-3p and miR-652-3p are linked to scWAT insulin resistance independent of obesity and influence insulin-stimulated lipogenesis by interacting at different steps with insulin-signaling pathways. (Source: AJP: Endocrinology and Metabolism)
Source: AJP: Endocrinology and Metabolism - June 1, 2017 Category: Endocrinology Authors: Dahlman, I., Belarbi, Y., Laurencikiene, J., Pettersson, A. M., Arner, P., Kulyte, A. Tags: Research Article Source Type: research
S100B impairs glycolysis via enhanced poly(ADP-ribosyl)ation of glyceraldehyde-3-phosphate dehydrogenase in rodent muscle cells
S100 calcium-binding protein B (S100B), a multifunctional macromolecule mainly expressed in nerve tissues and adipocytes, has been suggested to contribute to the pathogenesis of obesity. To clarify the role of S100B in insulin action and glucose metabolism in peripheral tissues, we investigated the effect of S100B on glycolysis in myoblast and myotube cells. Rat myoblast L6 cells were treated with recombinant mouse S100B to examine glucose consumption, lactate production, glycogen accumulation, glycolytic metabolites and enzyme activity, insulin signaling, and poly(ADP-ribosyl)ation of glyceraldehyde-3-phosphate dehydrogen...
Source: AJP: Endocrinology and Metabolism - June 1, 2017 Category: Endocrinology Authors: Hosokawa, K., Hamada, Y., Fujiya, A., Murase, M., Maekawa, R., Niwa, Y., Izumoto, T., Seino, Y., Tsunekawa, S., Arima, H. Tags: Research Article Source Type: research
{alpha}-Linolenic acid supplementation and exercise training reveal independent and additive responses on hepatic lipid accumulation in obese rats
α-Linolenic acid (ALA) supplementation or exercise training can independently prevent hepatic lipid accumulation and reduced insulin signaling; however, this may occur through different mechanisms of action. In the current study, obese Zucker rats displayed decreased phospholipid (PL) content in association with hepatic lipid abundance, and therefore, we examined whether ALA and exercise training would prevent these abnormalities differently to reveal additive effects on the liver. To achieve this aim, obese Zucker rats were fed control diet alone or supplemented with ALA and were sedentary or exercise trained for 4 ...
Source: AJP: Endocrinology and Metabolism - June 1, 2017 Category: Endocrinology Authors: Miotto, P. M., Horbatuk, M., Proudfoot, R., Matravadia, S., Bakovic, M., Chabowski, A., Holloway, G. P. Tags: Research Article Source Type: research
Ovarian functions role during cancer cachexia progression in the female mouse
In conclusion, our results provide evidence for a relationship between ovarian reproductive function and cachexia progression in female ApcMin/+ mice. (Source: AJP: Endocrinology and Metabolism)
Source: AJP: Endocrinology and Metabolism - May 15, 2017 Category: Endocrinology Authors: Hetzler, K. L., Hardee, J. P., LaVoie, H. A., Murphy, E. A., Carson, J. A. Tags: Research Article Source Type: research
Muscle PGC-1{alpha} is required for long-term systemic and local adaptations to a ketogenic diet in mice
Low-carbohydrate/high-fat (LCHF) diets are increasingly popular dietary interventions for body weight control and as treatment for different pathological conditions. However, the mechanisms of action are still poorly understood, in particular, in long-term administration. Besides liver, brain, and heart, skeletal muscle is one of the major organs involved in the regulation of physiological and pathophysiological ketosis. We assessed the role of the peroxisome proliferator-activated receptor coactivator 1α (PGC-1α) in skeletal muscle of male wild-type control and PGC-1α muscle-specific knockout mice upon 1...
Source: AJP: Endocrinology and Metabolism - May 15, 2017 Category: Endocrinology Authors: Schnyder, S., Svensson, K., Cardel, B., Handschin, C. Tags: Research Article Source Type: research
Insulin resistance and normal thyroid hormone levels: prospective study and metabolomic analysis
While hyperthyroidism and hypothyroidism cause dysglycemia, the relationship between thyroid hormone levels within the normal range and insulin resistance (IR) is unclear. In 940 participants with strictly normal serum concentrations of free triiodothyronine (fT3), free thyroxine (fT4), and thyroid-stimulating hormone (TSH) followed up for 3 yr, we measured insulin sensitivity (by the insulin clamp technique) and 35 circulating metabolites. At baseline, across quartiles of increasing fT3 levels (or fT3/fT4 ratio) most features of IR emerged [i.e., male sex, greater body mass index (BMI), waist circumference, heart rate, bl...
Source: AJP: Endocrinology and Metabolism - May 15, 2017 Category: Endocrinology Authors: Ferrannini, E., Iervasi, G., Cobb, J., Ndreu, R., Nannipieri, M. Tags: Research Article Source Type: research
Role of autonomic nervous system in chronic CNS-mediated antidiabetic action of leptin
This study tested whether ganglionic blockade or hepatic vagotomy attenuates the chronic central nervous system (CNS)-mediated antidiabetic and cardiovascular effects of leptin. Male Sprague-Dawley rats were instrumented with telemetry probes and arterial and venous catheters for determination of blood pressure (BP), heart rate (HR), blood sampling, and intravenous (iv) infusions. An intracerebroventricular (ICV) cannula was placed into the brain lateral ventricle for infusion of leptin or vehicle. After control measurements, streptozotocin (STZ) was injected iv (50 mg/kg) to induce diabetes, and 5 days later leptin (n = 6...
Source: AJP: Endocrinology and Metabolism - May 3, 2017 Category: Endocrinology Authors: da Silva, A. A., Hall, J. E., Moak, S. P., Browning, J., Houghton, H. J., Micheloni, G. C., do Carmo, J. M. Tags: Research Article Source Type: research
A model of chronic diabetic polyneuropathy: benefits from intranasal insulin are modified by sex and RAGE deletion
Human diabetic polyneuropathy (DPN) is a progressive complication of chronic diabetes mellitus. Preliminary evidence has suggested that intranasal insulin, in doses insufficient to alter hyperglycemia, suppresses the development of DPN. In this work we confirm this finding, but demonstrate that its impact is modified by sex and deletion of RAGE, the receptor for advanced glycosylation end products. We serially evaluated experimental DPN in male and female wild-type mice and male RAGE null (RN) mice, each with nondiabetic controls, during 16 wk of diabetes, the final 8 wk including groups given intranasal insulin. Age-match...
Source: AJP: Endocrinology and Metabolism - May 3, 2017 Category: Endocrinology Authors: de la Hoz, C. L., Cheng, C., Fernyhough, P., Zochodne, D. W. Tags: Research Article Source Type: research
Skeletal muscle PGC-1{beta} signaling is sufficient to drive an endurance exercise phenotype and to counteract components of detraining in mice
Peroxisome proliferator-activated receptor- coactivator (PGC)-1α and -1β serve as master transcriptional regulators of muscle mitochondrial functional capacity and are capable of enhancing muscle endurance when overexpressed in mice. We sought to determine whether muscle-specific transgenic overexpression of PGC-1β affects the detraining response following endurance training. First, we established and validated a mouse exercise-training-detraining protocol. Second, using multiple physiological and gene expression end points, we found that PGC-1β overexpression in skeletal muscle of sedentary mice fully...
Source: AJP: Endocrinology and Metabolism - May 3, 2017 Category: Endocrinology Authors: Lee, S., Leone, T. C., Rogosa, L., Rumsey, J., Ayala, J., Coen, P. M., Fitts, R. H., Vega, R. B., Kelly, D. P. Tags: Research Article Source Type: research
Loss of macrophage fatty acid oxidation does not potentiate systemic metabolic dysfunction
Fatty acid oxidation in macrophages has been suggested to play a causative role in high-fat diet-induced metabolic dysfunction, particularly in the etiology of adipose-driven insulin resistance. To understand the contribution of macrophage fatty acid oxidation directly to metabolic dysfunction in high-fat diet-induced obesity, we generated mice with a myeloid-specific knockout of carnitine palmitoyltransferase II (CPT2 M-KO), an obligate step in mitochondrial long-chain fatty acid oxidation. While fatty acid oxidation was clearly induced upon IL-4 stimulation, fatty acid oxidation-deficient CPT2 M-KO bone marrow-derived ma...
Source: AJP: Endocrinology and Metabolism - May 1, 2017 Category: Endocrinology Authors: Gonzalez-Hurtado, E., Lee, J., Choi, J., Selen Alpergin, E. S., Collins, S. L., Horton, M. R., Wolfgang, M. J. Tags: Research Article Source Type: research
Timing of meals: when is as critical as what and how much
Over the past decade, a large body of literature has demonstrated that disruptions of the endogenous circadian clock, whether environmental or genetic, lead to metabolic dysfunctions that are associated with obesity, diabetes, and other metabolic disorders. The phrase, "It is not only what you eat and how much you eat, but also when you eat" sends a simple message about circadian timing and body weight regulation. Communicating this message to clinicians and patients, while also elucidating the neuroendocrine, molecular, and genetic mechanisms underlying this phrase is essential to embrace the growing knowledge of the circ...
Source: AJP: Endocrinology and Metabolism - May 1, 2017 Category: Endocrinology Authors: Jiang, P., Turek, F. W. Tags: Review Source Type: research
Liver X receptor {alpha} induces 17{beta}-hydroxysteroid dehydrogenase-13 expression through SREBP-1c
Liver X receptors, including LXRα and LXRβ, are known to be master regulators of liver lipid metabolism. Activation of LXRα increases hepatic lipid storage in lipid droplets (LDs). 17β-Hydroxysteroid dehydrogenase-13 (17β-HSD13), a recently identified liver-specific LD-associated protein, has been reported to be involved in the development of nonalcoholic fatty liver disease. However, little is known about its transcriptional regulation. In the present study, we aimed at determining whether 17β-HSD13 gene transcription is controlled by LXRs. We found that treatment with T0901317, a nonspecif...
Source: AJP: Endocrinology and Metabolism - April 4, 2017 Category: Endocrinology Authors: Su, W., Peng, J., Li, S., Dai, Y.-b., Wang, C.-j., Xu, H., Gao, M., Ruan, X.-z., Gustafsson, J.-A., Guan, Y.-f., Zhang, X.-y. Tags: Research Article Source Type: research
Cardiovascular benefits associated with higher dietary K+ vs. lower dietary Na+: evidence from population and mechanistic studies
The World Health Organization ranks hypertension the leading global risk factor for disease, specifically, cardiovascular disease. Blood pressure (BP) is higher in Westernized populations consuming Na+-rich processed foods than in isolated societies consuming K+-rich natural foods. Evidence suggests that lowering dietary Na+ is particularly beneficial in hypertensive individuals who consume a high-Na+ diet. Nonetheless, numerous population studies demonstrate a relationship between higher dietary K+, estimated from urinary excretion or dietary recall, and lower BP, regardless of Na+ intake. Interventional studies with K+ s...
Source: AJP: Endocrinology and Metabolism - April 4, 2017 Category: Endocrinology Authors: McDonough, A. A., Veiras, L. C., Guevara, C. A., Ralph, D. L. Tags: Review Source Type: research
Deconstructing metabolic inflammation using cellular systems
Over the past years, we have embarked in a systematic analysis of the effect of obesity or fatty acids on circulating monocytes, microvascular endothelial cells, macrophages, and skeletal muscle cells. With the use of cell culture strategies, we have deconstructed complex physiological systems and then reconstructed "partial equations" to better understand cell-to-cell communication. Through these approaches, we identified that in high saturated fat environments, cell-autonomous proinflammatory pathways are activated in monocytes and endothelial cells, promoting monocyte adhesion and transmigration. We think of this as a p...
Source: AJP: Endocrinology and Metabolism - April 4, 2017 Category: Endocrinology Authors: Chan, K. L., Boroumand, P., Milanski, M., Pillon, N. J., Bilan, P. J., Klip, A. Tags: Review Source Type: research
