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American Journal of Physiology. Endocrinology and Metabolism

Evelyn Jantscher-Krenn, Johanna Aigner, Birgit Reiter, Harald Köfeler, Bence Csapo, Gernot Desoye, Lars Bode, Mireille N M Van Poppel
Human Milk Oligosaccharides (HMOs) are bioactive glycans linked with health benefits to both, breastfed infant and lactating mother. We hypothesized that HMOs are present prior to lactation, already during pregnancy, and are influenced by maternal body composition. In a pilot study, we investigated individual and temporal variations in HMO composition and concentration in maternal serum at gestational weeks 10-14, 20-24, and 30-35 (V1, V2, and V3, respectively), and associations with maternal body composition...
November 13, 2018: American Journal of Physiology. Endocrinology and Metabolism
Joshua A Kulas, Whitney Franklin, Nicholas A Smith, Gunjan D Manocha, Kendra L Puig, Kumi Nagamoto-Combs, Rachel D Hendrix, Giulio Taglialatela, Steven W Barger, Colin K Combs
The amyloid precursor protein (APP) is a type-I transmembrane glycoprotein widely studied for its role as the source of β-amyloid peptide, accumulation of which is causal in at least some cases of Alzheimer's disease (AD). APP is expressed ubiquitously and is involved in diverse biological processes. Growing bodies of evidence indicate connections between AD and somatic metabolic disorders related to type-2 diabetes, and App-/- mice show alterations in glycemic regulation. We find that App-/- have higher levels of insulin-degrading enzyme (IDE) mRNA, protein, and activity compared to wild-type controls...
November 13, 2018: American Journal of Physiology. Endocrinology and Metabolism
Shi-Jun Yue, Juan Liu, Ai-Ting Wang, Xin-Tong Meng, Zhi-Rui Yang, Cheng Peng, Hua-Shi Guan, Chang-Yun Wang, Dan Yan
Increased circulating branched-chain amino acids (BCAAs) have been involved in the pathogenesis of obesity and insulin resistance (IR). However, evidence relating berberine (BBR), gut microbiota, BCAAs and IR is limited. Here, we showed that BBR could effectively rectify steatohepatitis and glucose intolerance in high-fat diet (HFD)-fed mice. BBR reorganized gut microbiota populations under both the normal chow diet (NCD) and HFD. Particularly, BBR noticeably decreased the relative abundance of BCAA-producing bacteria, including order Clostridiales, families Streptococcaceae, Clostridiaceae and Prevotellaceae, and genera Streptococcus and Prevotella...
November 13, 2018: American Journal of Physiology. Endocrinology and Metabolism
Johannes Kettunen, Anni Joensuu, Maria Hagnäs, Ilona Mikkola, Annika Wennerström, Joseph H Lee, Joseph D Terwilliger, Katja Borodulin, Pekka Jousilahti, Matti Jauhiainen, Jari J Jokelainen, Sirkka Keinänen-Kiukaanniemi, Markus Perola
Higher physical activity is associated with a reduced hazard for a plethora of diseases. It has remained unknown how the two primary physical activity associated health effects, improved physical performance and change in body composition, independently modulate metabolic profiles towards a reduced risk for adverse outcomes.Here, we utilized a prospective cohort of 664 young men undergoing military service. We studied the metabolic associations of changes in muscle performance and body composition during military service (range 6-12 months)...
November 13, 2018: American Journal of Physiology. Endocrinology and Metabolism
Mercedes Clemente-Postigo, Wilfredo Oliva-Olivera, Leticia Coin-Araguez, Bruno Ramos-Molina, Rosa Maria Giraldez-Perez, Said Lhamyani, Juan Alcaide-Torres, Pablo Perez-Martinez, Rajaa El-Bekay, Fernando Cardona, Francisco J Tinahones
Impaired adipose tissue (AT) lipid handling and inflammation is associated with obesity-related metabolic diseases. Circulating lipopolysaccharides (LPS) from gut microbiota (metabolic endotoxemia), proposed as a triggering factor for the low-grade inflammation in obesity, might also be the responsible for AT dysfunction. Nevertheless, this hypothesis has not been explored in human obesity. In order to analyze the relationship between metabolic endotoxemia and AT markers for lipogenesis, lipid handling and inflammation in human obesity, 33 obese patients scheduled for surgery were recruited and classified according to their LPS levels...
November 13, 2018: American Journal of Physiology. Endocrinology and Metabolism
Jie Zhang, Sudeepa Bhattacharyya, Robert C Hickner, Alan R Light, Christopher J Lambert, Bruce K Gale, Oliver Fiehn, Sean H Adams
Blood or biopsies are often applied to characterize metabolites that are modulated by exercising muscle. However, blood has inputs derived from multiple tissues, biopsies cannot discriminate secreted vs. intracellular metabolites and their invasive nature is challenging for frequent collections in sensitive populations (e.g., children, pregnant women). Thus, minimally-invasive approaches to interstitial fluid (IF) metabolomics would be valuable. A catheter was designed to collect gastrocnemius IF from acutely anesthetized adult male rats, at rest or immediately following 20 min...
November 6, 2018: American Journal of Physiology. Endocrinology and Metabolism
Eugenia Mata-Greenwood, Hillary F Huber, Cun Li, Peter W Nathanielsz
INTRODUCTION: Human studies show that obesity is associated with vitamin D insufficiency, which contributes to obesity-related disorders. Our aim was to elucidate the regulation of vitamin D during pregnancy and obesity in a non-human primate species. METHODS: We studied lean and obese non-pregnant and pregnant baboons. Plasma 25-OH-D and 1α,25-(OH)2 -D metabolites were analyzed using ELISA. Vitamin D-related gene expression was studied in maternal kidney, liver, subcutaneous fat, and placental tissue using real-time PCR and immunoblotting...
November 6, 2018: American Journal of Physiology. Endocrinology and Metabolism
Yang Chen, Mingyue Zhao, Tingting Zheng, Salah Adlat, Honghong Jin, Chenhao Wang, Dan Li, May Zun Zaw Myint, Yapeng Yao, Liu Xu, Mingjun San, Huaizhen Wen, Yuntao Zhang, Xiaodan Lu, Ling Yang, Luqing Zhang, Xuechao Feng, Yaowu Zheng
Obesity is the results of excessive energy accumulation and associated with many diseases. We previously reported that universal repression of vascular endothelial growth factor (VEGF) leads to brown-like adipocyte development in white adipose tissues and mice are resistant to obesity. Using an adipose-specific VEGF repression mouse model (aP2-rtTR-krabtg/+ /VEGFtetO/tetO ), we show that adipose-specific VEGF repression can repeat the previous phenotypes including adipose browning, increased energy consumption and reduction in body weight...
November 6, 2018: American Journal of Physiology. Endocrinology and Metabolism
Beatriz C Borges, Xingfa Han, Susan J Allen, David Garcia-Galiano, Carol F Elias
Hypothalamic neurons detect changes in circulating hormones such as leptin and insulin and put forward outputs to sustain energy and glucose homeostasis. Because leptin and insulin receptors colocalize in about 40-60% of neurons in the hypothalamus, we characterized the metabolic phenotype of mice with selective deletion of the InsR in LepR cells. LRΔInsR mice presented no difference in body weight and insulin levels, but increased fat mass. In the light phase, LRΔInsR mice exhibited increased food intake, locomotor activity, VCO2 and RER...
October 30, 2018: American Journal of Physiology. Endocrinology and Metabolism
Donghua Hu, Ryan D Russell, Devika Remash, Timothy Greenaway, Stephen Rattigan, Kathryn A Squibb, Graeme Jones, Renee M Ross, Christian K Roberts, Dino Premilovac, Stephen M Richards, Michelle A Keske
The microcirculation in adipose tissue is markedly impaired in type 2 diabetes (T2D). Resistance training (RT) often increases muscle mass and promotes a favourable metabolic profile in people with T2D, even in the absence of fat loss. Whether the metabolic benefits of RT in T2D are linked to improvements in adipose tissue microvascular blood flow is unknown. Eighteen sedentary people with T2D (7F/11M, 52±7 years) completed six weeks of RT. Before and after RT, overnight-fasted participants had blood sampled for clinical chemistries (glucose, insulin, lipids, HbA1c and pro-inflammatory markers), underwent an oral glucose challenge (OGC, 50g glucose x 2hr) and a DEXA scan to assess body composition...
October 23, 2018: American Journal of Physiology. Endocrinology and Metabolism
Samantha R Weaver, Hannah P Fricke, Cynthia Xie, Robert J Aiello, Julia F Charles, Laura L Hernandez
Long-term effects of breastfeeding on maternal bone are not fully understood. Excessive maternal bone loss stimulated by serotonin signaling during lactation may increase bone fragility later in life. We hypothesized inhibiting non-neuronal serotonin activity by feeding a small molecule inhibitor of the rate-limiting enzyme in serotonin synthesis (tryptophan hydroxylase 1; TPH1) would preserve maternal bone post-weaning without affecting neonatal bone. Small molecule TPH1 inhibitor LP778902 (~100 mg/kg) or control chow was fed to C57BL/6 dams throughout pregnancy and lactation and blood collected on days 1 and 21 of lactation...
October 23, 2018: American Journal of Physiology. Endocrinology and Metabolism
Hasiyet Memetimin, Dong Li, Kaiyuan Tan, Changcheng Zhou, Ying Liang, Yadi Wu, Shuxia Wang
Thrombospondin 1 (TSP1) is a multifunctional matricellular protein. Recent studies demonstrate that TSP1 is highly expressed in adipose tissue (AT) and positively associated with AT inflammation and insulin resistance (IR). In this study, the contribution of different cellular sources of TSP1 to obesity-induced metabolic complications is determined by using mice with either adipocyte or myeloid/macrophage-specific deletion of TSP1 in a diet-induced obese model. The results demonstrated that neither adipocyte nor myeloid/macrophage-specific deletion of TSP1 affected the development of long-term high fat diet (HFD)-induced obesity...
October 23, 2018: American Journal of Physiology. Endocrinology and Metabolism
Vishva M Sharma, Esben Thyssen Vestergaard, Niels Jessen, Peter Kolind-Thomsen, Birgitte Nellemann, Thomas S Nielsen, Mikkel Holm Vendelbo, Niels Møller, Rita Sharma, Kevin Y Lee, John J Kopchick, Jens Otto Lunde Jørgensen, Vishwajeet Puri
The lipolytic effects of GH have been known for half a century and play an important physiological role for substrate metabolism during fasting. In addition, sustained GH-induced lipolysis is causally linked to insulin resistance. However, the underlying molecular mechanisms remain elusive. In the present study, we obtained experimental data in human subjects and used human adipose-derived stromal vascular cells (hADSCs) as a model system to elucidate GH-triggered molecular signaling that stimulates adipose tissue lipolysis and insulin resistance in human adipocytes...
October 16, 2018: American Journal of Physiology. Endocrinology and Metabolism
Thiago Gagliano-Jucá, Karol M Pencina, Tomas Ganz, Thomas G Travison, Philip W Kantoff, Paul L Nguyen, Mary-Ellen Taplin, Adam S Kibel, Zhuoying Li, Grace Huang, Robert R Edwards, Elizabeta Nemeth, Shehzad Basaria
Androgen deprivation therapy (ADT) is a mainstay of treatment for prostate cancer (PCa). As androgens stimulate erythropoiesis, ADT is associated with a reduction in hematocrit, which in turn contributes to fatigue and related morbidity. However, the mechanisms involved in ADT-induced reduction in erythropoiesis remain unclear. We conducted a 6-month prospective cohort study and enrolled men with PCa about to undergo ADT (ADT-Group) and a control group of men who had previously undergone prostatectomy for localized PCa and were in remission (Non-ADT Group)...
October 16, 2018: American Journal of Physiology. Endocrinology and Metabolism
Ursula H Neumann, Michelle M Kwon, Robert K Baker, Timothy J Kieffer
It was long thought that the only hormone capable of reversing the catabolic consequences of diabetes was insulin. However, various studies have demonstrated that the adipocyte-derived hormone leptin can robustly lower blood glucose levels in rodent models of insulin-deficient diabetes. In addition, it has been suggested that some of the metabolic manifestations of insulin-deficient diabetes are due to hypoleptinemia as opposed to hypoinsulinemia. Since insulin therapy increases leptin levels, we sought to investigate the contribution of leptin to the beneficial effects of insulin therapy...
October 9, 2018: American Journal of Physiology. Endocrinology and Metabolism
Jacquelyn M Walejko, Jeremy P Koelmel, Timothy J Garrett, Arthur S Edison, Maureen Keller-Wood
During late gestation, the fetal heart primarily relies on glucose and lactate to support rapid growth and development. While numerous studies describe changes in heart metabolism to preferentially utilize fatty acids a few weeks after birth, little is known about metabolic changes of the heart within the first day following birth. Therefore, we used the ovine model of pregnancy to investigate metabolic differences between the near-term fetal and the newborn heart. Heart tissue was collected for metabolomic, lipidomic, and transcriptomic approaches from the left and right ventricles and intraventricular septum in 7 fetuses at gestational day 142 and 7 newborn lambs on the day of birth...
October 9, 2018: American Journal of Physiology. Endocrinology and Metabolism
Justin Loloi, Amanda J Miller, Sarah S Bingaman, Yuval Silberman, Amy C Arnold
Angiotensin converting enzyme (ACE) inhibitors reduce body weight, lower blood pressure (BP), and improve insulin sensitivity in animal models of cardiometabolic syndrome. These effects are generally attributed to reduced angiotensin (Ang) II formation; however, these therapies also increase levels of Ang-(1-7), a beneficial hormone opposing Ang II actions. We hypothesized this Ang-(1-7) generation contributes to the insulin sensitizing effects of ACE inhibition in obese mice. Adult male C57BL/6J mice were placed on a 60% high fat diet for 11 weeks...
October 9, 2018: American Journal of Physiology. Endocrinology and Metabolism
Liping Qiao, Samuel Lee, Amanda Nguyen, William W Hay, Jianhua Shao
To determine the role of UCP1-mediated thermogenesis in controlling maternal metabolic adaptation to pregnancy, energy metabolism of C57BL/6 wild-type (WT) and Ucp1 gene knockout (Ucp1-/- ) mice was studied during pregnancy. With the progression of pregnancy, maternal energy expenditure rates (EERs), expression of UCP1 and core body temperature steadily declined in WT dams. Despite no significant alterations in core body temperature and weight gain during pregnancy, Ucp1-/- dams exhibited lower rates in EER decline...
October 2, 2018: American Journal of Physiology. Endocrinology and Metabolism
Liam McAllan, Kristen R Maynard, Alisha S Kardian, Amanda S Stayton, Shelby L Fox, Erin J Stephenson, Clint E Kinney, Noor K Alshibli, Charles K Gomes, Joseph F Pierre, Michelle A Puchowicz, Dave Bridges, Keri Martinowich, Joan C Han
Brain-derived neurotrophic factor (BDNF) is a key neuropeptide in the central regulation of energy balance. The Bdnf gene contains nine promoters, each producing specific mRNA transcripts that encode a common protein. We sought to assess the phenotypic outcomes of disrupting BDNF production from individual Bdnf promoters. Mice with an intact coding region but selective disruption of BDNF production from Bdnf promoters I, II, IV or VI (Bdnf-e1-/- , -e2-/- , -e4-/- , and -e6-/- ) were created by inserting a GFP-STOP cassette upstream of the targeted promoter splice donor site...
September 25, 2018: American Journal of Physiology. Endocrinology and Metabolism
Louise Grahnemo, Karin Gustafsson, Klara Sjogren, Petra Henning, Vikte Lionikaite, Antti Koskela, Juha Tuukkanen, Claes Ohlsson, Ingrid Wernstedt Asterholm, Marie K Lagerquist
Mice with impaired acute inflammatory responses within adipose tissue display reduced diet-induced fat mass gain associated with glucose intolerance and systemic inflammation. Therefore, acute adipose tissue inflammation is needed for a healthy expansion of adipose tissue. Because inflammatory disorders are associated with bone loss, we hypothesized that impaired acute adipose tissue inflammation leading to increased systemic inflammation results in a lower bone mass. To test this hypothesis, we used mice overexpressing an adenoviral protein complex - the receptor internalization and degradation (RID) complex that inhibits pro-inflammatory signaling - under the control of the aP2-promotor (RID tg mice), resulting in suppressed inflammatory signaling in adipocytes...
September 25, 2018: American Journal of Physiology. Endocrinology and Metabolism
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