Low-dose leptin infusion in the fourth ventricle of rats enhances the response to third-ventricle leptin injection
We previously reported that low-dose leptin infusions into the third or fourth ventricle that do not affect energy balance when given independently cause rapid weight loss when given simultaneously. Therefore, we tested whether hindbrain leptin enhances the response to forebrain leptin or whether forebrain leptin enhances the response to hindbrain leptin. Rats received fourth-ventricle infusions of saline or 0.01, 0.1, 0.3, or 0.6 μg leptin/day for 13 days. On days 9 and 13, 0.1 μg leptin was injected into the third ventricle. The injection inhibited food intake for 36 h in saline-infused rats but for 60 h in those i...
Source: AJP: Endocrinology and Metabolism - August 1, 2017 Category: Endocrinology Authors: Harris, R. B. S. Tags: Research Article Source Type: research

Cyp8b1 ablation prevents Western diet-induced weight gain and hepatic steatosis because of impaired fat absorption
Bile acids (BAs) are cholesterol derivatives that regulate lipid metabolism, through their dual abilities to promote lipid absorption and activate BA receptors. However, different BA species have varying abilities to perform these functions. Eliminating 12α-hydroxy BAs in mice via Cyp8b1 knockout causes low body weight and improved glucose tolerance. The goal of this study was to determine mechanisms of low body weight in Cyp8b1–/– mice. We challenged Cyp8b1–/– mice with a Western-type diet and assessed body weight and composition. We measured energy expenditure, fecal calories, and lipid abso...
Source: AJP: Endocrinology and Metabolism - August 1, 2017 Category: Endocrinology Authors: Bertaggia, E., Jensen, K. K., Castro-Perez, J., Xu, Y., Di Paolo, G., Chan, R. B., Wang, L., Haeusler, R. A. Tags: Research Article Source Type: research

Western-diet consumption induces alteration of barrier function mechanisms in the ileum that correlates with metabolic endotoxemia in rats
Obesity and its related disorders have been associated with the presence in the blood of gut bacteria-derived lipopolysaccharides (LPS). However, the factors underlying this low-grade elevation in plasma LPS, so-called metabolic endotoxemia, are not fully elucidated. We aimed to investigate the effects of Western diet (WD) feeding on intestinal and hepatic LPS handling mechanisms in a rat model of diet-induced obesity (DIO). Rats were fed either a standard chow diet (C) or a Western Diet (WD, 45% fat) for 6 wk. They were either fed ad libitum or pair-fed to match the caloric intake of C rats for the first week, then fed ad...
Source: AJP: Endocrinology and Metabolism - August 1, 2017 Category: Endocrinology Authors: Guerville, M., Leroy, A., Sinquin, A., Laugerette, F., Michalski, M.-C., Boudry, G. Tags: Research Article Source Type: research

Retraction
(Source: AJP: Endocrinology and Metabolism)
Source: AJP: Endocrinology and Metabolism - July 7, 2017 Category: Endocrinology Authors: Pasek, R. C., Dunn, J. C., Elsakr, J. M., Aramandla, M., Matta, A. R., Gannon, M. Tags: Retraction Source Type: research

Oxygen delivery and the restoration of the muscle energetic balance following exercise: implications for delayed muscle recovery in patients with COPD
Patients with chronic obstructive pulmonary disease (COPD) experience a delayed recovery from skeletal muscle fatigue following exhaustive exercise that likely contributes to their progressive loss of mobility. As this phenomenon is not well understood, this study sought to examine postexercise peripheral oxygen (O2) transport and muscle metabolism dynamics in patients with COPD, two important determinants of muscle recovery. Twenty-four subjects, 12 nonhypoxemic patients with COPD and 12 healthy subjects with a sedentary lifestyle, performed dynamic plantar flexion exercise at 40% of the maximal work rate (WRmax) with pho...
Source: AJP: Endocrinology and Metabolism - July 7, 2017 Category: Endocrinology Authors: Layec, G., Hart, C. R., Trinity, J. D., Kwon, O.-S., Rossman, M. J., Broxterman, R. M., Le Fur, Y., Jeong, E.-K., Richardson, R. S. Tags: Research Article Source Type: research

Feeding influences adipose tissue responses to exercise in overweight men
Feeding profoundly affects metabolic responses to exercise in various tissues, but the effect of feeding status on human adipose tissue responses to exercise has never been studied. Ten healthy overweight men aged 26 ± 5 yr (mean ± SD) with a waist circumference of 105 ± 10 cm walked at 60% of maximum oxygen uptake under either fasted or fed conditions in a randomized, counterbalanced design. Feeding comprised 648 ± 115 kcal 2 h before exercise. Blood samples were collected at regular intervals to examine changes in metabolic parameters and adipokine concentrations. Adipose tissue samples were o...
Source: AJP: Endocrinology and Metabolism - July 7, 2017 Category: Endocrinology Authors: Chen, Y.-C., Travers, R. L., Walhin, J.-P., Gonzalez, J. T., Koumanov, F., Betts, J. A., Thompson, D. Tags: Research Article Source Type: research

Does maternal-fetal transfer of creatine occur in pregnant sheep?
Our aim was to determine the disposition of creatine in ovine pregnancy and whether creatine is transferred across the placenta from mother to fetus. Pregnant ewes received either 1) a continuous intravenous infusion of creatine monohydrate or saline from 122 to 131 days gestation, with maternal and fetal arterial blood and amniotic fluid samples collected daily for creatine analysis and fetal tissues collected at necropsy at 133 days for analysis of creatine content, or 2) a single systemic bolus injection of [13C]creatine monohydrate at 130 days of gestation, with maternal and fetal arterial blood, uterine vein blood, an...
Source: AJP: Endocrinology and Metabolism - July 1, 2017 Category: Endocrinology Authors: Baharom, S., De Matteo, R., Ellery, S., Della Gatta, P., Bruce, C. R., Kowalski, G. M., Hale, N., Dickinson, H., Harding, R., Walker, D., Snow, R. J. Tags: Research Article Source Type: research

A four-compartment compartmental model to assess net whole body protein breakdown using a pulse of phenylalanine and tyrosine stable isotopes in humans
The stable isotopes of phenylalanine (Phe) and tyrosine (Tyr) are often used to study whole body protein metabolism in humans. Noncompartmental approaches give limited physiological insight in the compartmental characteristics. We therefore developed a compartmental mathematical model of Phe/Tyr metabolism to describe protein fluxes by using stable tracer dynamic data in plasma following intravenous bolus of l-[ring-13C6]Phe and l-[ring-2H4]Tyr in healthy subjects. The model consists of four compartments describing Phe/Tyr kinetics. Because the model is a priori nonidentifiable, it is quantified in terms of two uniquely id...
Source: AJP: Endocrinology and Metabolism - July 1, 2017 Category: Endocrinology Authors: Mason, A., Engelen, M. P. K. J., Ivanov, I., Toffolo, G. M., Deutz, N. E. P. Tags: Research Article Source Type: research

Effects of genetic deletion of soluble 5'-nucleotidases NT5C1A and NT5C2 on AMPK activation and nucleotide levels in contracting mouse skeletal muscles
AMP-activated protein kinase (AMPK) plays a key role in energy homeostasis and is activated in response to contraction-induced ATP depletion in skeletal muscle via a rise in intracellular AMP/ADP concentrations. AMP can be deaminated by AMP-deaminase (AMPD) to IMP, which is hydrolyzed to inosine by cytosolic 5'-nucleotidase II (NT5C2). AMP can also be hydrolyzed to adenosine by cytosolic 5'-nucleotidase 1A (NT5C1A). Previous gene silencing and overexpression studies indicated control of AMPK activation by NT5C enzymes. In the present study using gene knockout mouse models, we investigated the effects of NT5C1A and NT5C2 de...
Source: AJP: Endocrinology and Metabolism - July 1, 2017 Category: Endocrinology Authors: Kviklyte, S., Vertommen, D., Yerna, X., Andersen, H., Xu, X., Gailly, P., Bohlooly-Y, M., Oscarsson, J., Rider, M. H. Tags: Research Article Source Type: research

GPR40 reduces food intake and body weight through GLP-1
G protein-coupled receptor 40 (GPR40) partial agonists lower glucose through the potentiation of glucose-stimulated insulin secretion, which is believed to provide significant glucose lowering without the weight gain or hypoglycemic risk associated with exogenous insulin or glucose-independent insulin secretagogues. The class of small-molecule GPR40 modulators, known as AgoPAMs (agonist also capable of acting as positive allosteric modulators), differentiate from partial agonists, binding to a distinct site and functioning as full agonists to stimulate the secretion of both insulin and glucagon-like peptide-1 (GLP-1). Here...
Source: AJP: Endocrinology and Metabolism - July 1, 2017 Category: Endocrinology Authors: Gorski, J. N., Pachanski, M. J., Mane, J., Plummer, C. W., Souza, S., Thomas-Fowlkes, B. S., Ogawa, A. M., Weinglass, A. B., Di Salvo, J., Cheewatrakoolpong, B., Howard, A. D., Colletti, S. L., Trujillo, M. E. Tags: Research Article Source Type: research

Overactivation of the endocannabinoid system alters the antilipolytic action of insulin in mouse adipose tissue
This study indicates the existence of a functional interaction between CB1R and lipolysis regulation in AT. Further investigation is needed to test if the elevation of ECS tone encountered in obesity is associated with excess fat mobilization contributing to ectopic fat deposition and related metabolic disorders. (Source: AJP: Endocrinology and Metabolism)
Source: AJP: Endocrinology and Metabolism - July 1, 2017 Category: Endocrinology Authors: Muller, T., Demizieux, L., Troy-Fioramonti, S., Gresti, J., Pais de Barros, J.-P., Berger, H., Verges, B., Degrace, P. Tags: Research Article Source Type: research

Gonad-related factors promote muscle performance gain during postnatal development in male and female mice
To better define the role of male and female gonad-related factors (MGRF, presumably testosterone, and FGRF, presumably estradiol, respectively) on mouse hindlimb skeletal muscle contractile performance/function gain during postnatal development, we analyzed the effect of castration initiated before puberty in male and female mice. We found that muscle absolute and specific (normalized to muscle weight) maximal forces were decreased in 6-mo-old male and female castrated mice compared with age- and sex-matched intact mice, without alteration in neuromuscular transmission. Moreover, castration decreased absolute and specific...
Source: AJP: Endocrinology and Metabolism - July 1, 2017 Category: Endocrinology Authors: Ueberschlag-Pitiot, V., Stantzou, A., Messeant, J., Lemaitre, M., Owens, D. J., Noirez, P., Roy, P., Agbulut, O., Metzger, D., Ferry, A. Tags: Research Article Source Type: research

Whey protein effects on energy balance link the intestinal mechanisms of energy absorption with adiposity and hypothalamic neuropeptide gene expression
We tested the hypothesis that dietary whey protein isolate (WPI) affects the intestinal mechanisms related to energy absorption and that the resulting energy deficit is compensated by changes in energy balance to support growth. C57BL/6 mice were provided a diet enriched with WPI with varied sucrose content, and the impact on energy balance-related parameters was investigated. As part of a high-sucrose diet, WPI reduced the hypothalamic expression of pro-opiomelanocortin gene expression and increased energy intake. The energy expenditure was unaffected, but epididymal weight was reduced, indicating an energy loss. Notably,...
Source: AJP: Endocrinology and Metabolism - July 1, 2017 Category: Endocrinology Authors: Nilaweera, K. N., Cabrera-Rubio, R., Speakman, J. R., OConnor, P. M., McAuliffe, A., Guinane, C. M., Lawton, E. M., Crispie, F., Aguilera, M., Stanley, M., Boscaini, S., Joyce, S., Melgar, S., Cryan, J. F., Cotter, P. D. Tags: Research Article Source Type: research

Phenylalanine isotope pulse method to measure effect of sepsis on protein breakdown and membrane transport in the pig
The primed-continuous (PC) phenylalanine (Phe) stable isotope infusion methodology is often used as a proxy for measuring whole body protein breakdown (WbPB) in sepsis. It is unclear if WbPB data obtained by an easy-to-use single IV Phe isotope pulse administration (PULSE) are comparable to those by PC. Compartmental modeling with PULSE could provide us more insight in WbPB in sepsis. Therefore, in the present study, we compared PULSE with PC as proxy for WbPB in an instrumented pig model with Pseudomonas aeruginosa-induced severe sepsis (Healthy: n = 9; Sepsis: n = 13). Seventeen hours after sepsis induction, we compared ...
Source: AJP: Endocrinology and Metabolism - June 4, 2017 Category: Endocrinology Authors: Ten Have, G. A. M., Engelen, M. P. K. J., Wolfe, R. R., Deutz, N. E. P. Tags: Research Article Source Type: research

The {beta}3-adrenergic receptor is dispensable for browning of adipose tissues
Brown and brite/beige adipocytes are attractive therapeutic targets to treat metabolic diseases. To maximally utilize their functional potential, further understanding is required about their identities and their functional differences. Recent studies with β3-adrenergic receptor knockout mice reported that brite/beige adipocytes, but not classical brown adipocytes, require the β3-adrenergic receptor for cold-induced transcriptional activation of thermogenic genes. We aimed to further characterize this requirement of the β3-adrenergic receptor as a functional distinction between classical brown and brite/beig...
Source: AJP: Endocrinology and Metabolism - June 4, 2017 Category: Endocrinology Authors: de Jong, J. M. A., Wouters, R. T. F., Boulet, N., Cannon, B., Nedergaard, J., Petrovic, N. Tags: Research Article Source Type: research