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Molecular Metabolism

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https://www.readbyqxmd.com/read/29455954/the-peroxisome-proliferator-activated-receptor-%C3%AE-is-dispensable-for-cold-induced-adipose-tissue-browning-in-mice
#1
Merel Defour, Wieneke Dijk, Philip Ruppert, Emmani B M Nascimento, Patrick Schrauwen, Sander Kersten
OBJECTIVE: Chronic cold exposure causes white adipose tissue (WAT) to adopt features of brown adipose tissue (BAT), a process known as browning. Previous studies have hinted at a possible role for the transcription factor Peroxisome Proliferator-Activated Receptor alpha (PPARα) in cold-induced browning. Here we aimed to investigate the importance of PPARα in driving transcriptional changes during cold-induced browning in mice. METHODS: Male wildtype and PPARα-/- mice were housed at thermoneutrality (28 °C) or cold (5 °C) for 10 days...
February 9, 2018: Molecular Metabolism
https://www.readbyqxmd.com/read/29472102/modeling-human-pancreatic-beta-cell-dedifferentiation
#2
Marc Diedisheim, Masaya Oshima, Olivier Albagli, Charlotte Wennberg Huldt, Ingela Ahlstedt, Maryam Clausen, Suraj Menon, Alexander Aivazidis, Anne-Christine Andreasson, William G Haynes, Piero Marchetti, Lorella Marselli, Mathieu Armanet, Fabrice Chimienti, Raphael Scharfmann
OBJECTIVE: Dedifferentiation could explain reduced functional pancreatic β-cell mass in type 2 diabetes (T2D). METHODS: Here we model human β-cell dedifferentiation using growth factor stimulation in the human β-cell line, EndoC-βH1, and human pancreatic islets. RESULTS: Fibroblast growth factor 2 (FGF2) treatment reduced expression of β-cell markers, (INS, MAFB, SLC2A2, SLC30A8, and GCK) and activated ectopic expression of MYC, HES1, SOX9, and NEUROG3...
February 8, 2018: Molecular Metabolism
https://www.readbyqxmd.com/read/29459251/prolyl-carboxypeptidase-in-agouti-related-peptide-neurons-modulates-food-intake-and-body-weight
#3
Giuseppe Bruschetta, Sungho Jin, Jung Dae Kim, Sabrina Diano
OBJECTIVE: Prolyl carboxypeptidase (PRCP) plays a role in the regulation of energy metabolism by inactivating hypothalamic α-melanocyte stimulating hormone (α-MSH) levels. Although detected in the arcuate nucleus, limited PRCP expression has been observed in the arcuate POMC neurons, and its site of action in regulating metabolism is still ill-defined. METHODS: We performed immunostaining to assess the localization of PRCP in arcuate Neuropeptide Y/Agouti-related Peptide (NPY/AgRP) neurons...
February 8, 2018: Molecular Metabolism
https://www.readbyqxmd.com/read/29439854/rapid-sensing-of-l-leucine-by-human-and-murine-hypothalamic-neurons-neurochemical-and-mechanistic-insights
#4
Nicholas Heeley, Peter Kirwan, Tamana Darwish, Marion Arnaud, Mark L Evans, Florian T Merkle, Frank Reimann, Fiona M Gribble, Clemence Blouet
OBJECTIVE: Dietary proteins are sensed by hypothalamic neurons and strongly influence multiple aspects of metabolic health, including appetite, weight gain, and adiposity. However, little is known about the mechanisms by which hypothalamic neural circuits controlling behavior and metabolism sense protein availability. The aim of this study is to characterize how neurons from the mediobasal hypothalamus respond to a signal of protein availability: the amino acid l-leucine. METHODS: We used primary cultures of post-weaning murine mediobasal hypothalamic neurons, hypothalamic neurons derived from human induced pluripotent stem cells, and calcium imaging to characterize rapid neuronal responses to physiological changes in extracellular l-Leucine concentration...
February 7, 2018: Molecular Metabolism
https://www.readbyqxmd.com/read/29453154/unique-pharmacology-of-a-novel-allosteric-agonist-sensitizer-insulin-receptor-monoclonal-antibody
#5
Simon A Hinke, Anne M Cieniewicz, Thomas Kirchner, Katharine D'Aquino, Rupesh Nanjunda, Jason Aligo, Robert Perkinson, Philip Cooper, Ken Boayke, Mark L Chiu, Steve Jarantow, Eilyn R Lacy, Yin Liang, Dana L Johnson, Jean M Whaley, Russell B Lingham, Anthony J Kihm
OBJECTIVE: Insulin resistance is a key feature of Type 2 Diabetes (T2D), and improving insulin sensitivity is important for disease management. Allosteric modulation of the insulin receptor (IR) with monoclonal antibodies (mAbs) can enhance insulin sensitivity and restore glycemic control in animal models of T2D. METHODS: A novel human mAb, IRAB-A, was identified by phage screening using competition binding and surface plasmon resonance assays with the IR extracellular domain...
February 3, 2018: Molecular Metabolism
https://www.readbyqxmd.com/read/29428596/small-molecule-pgc-1%C3%AE-1-protein-stabilizers-induce-adipocyte-ucp1-expression-and-uncoupled-mitochondrial-respiration
#6
A T Pettersson-Klein, M Izadi, D M S Ferreira, I Cervenka, J C Correia, V Martinez-Redondo, M Southern, M Cameron, T Kamenecka, L Z Agudelo, M Porsmyr-Palmertz, U Martens, B Lundgren, M Otrocka, A Jenmalm-Jensen, P R Griffin, J L Ruas
OBJECTIVE: The peroxisome proliferator-activated receptor-γ coactivator-1α1 (PGC-1α1) regulates genes involved in energy metabolism. Increasing adipose tissue energy expenditure through PGC-1α1 activation is potentially beneficial for systemic metabolism. Pharmacological PGC-1α1 activators could be valuable tools in the fight against obesity and metabolic disease. Finding such compounds has been challenging partly because PGC-1α1 is a transcriptional coactivator with no known ligand-binding properties...
February 3, 2018: Molecular Metabolism
https://www.readbyqxmd.com/read/29398616/hypothalamic-mir-219-regulates-individual-metabolic-differences-in-response-to-diet-induced-weight-cycling
#7
Mariana Schroeder, Yonat Drori, Yair J Ben-Efraim, Alon Chen
Consumption of a low calorie diet is the most common approach to lose weight. While generally effective at first, it is frequently followed by a relapse where the pre-diet weight is regained, and often exceeded. This pattern of repeated weight loss/regain is referred to as weight cycling and the resulting metabolic response varies greatly between individuals. OBJECTIVE: We attempted to address the issue of individual differences in the response to weight cycling in male mice. METHODS: We first exposed adult wild type mice to repeated cycles of high/low fat food...
February 1, 2018: Molecular Metabolism
https://www.readbyqxmd.com/read/29398615/insulin-like-growth-factor-receptor-signaling-regulates-working-memory-mitochondrial-metabolism-and-amyloid-%C3%AE-uptake-in-astrocytes
#8
Sreemathi Logan, Gavin A Pharaoh, M Caleb Marlin, Dustin R Masser, Satoshi Matsuzaki, Benjamin Wronowski, Alexander Yeganeh, Eileen E Parks, Pavithra Premkumar, Julie A Farley, Daniel B Owen, Kenneth M Humphries, Michael Kinter, Willard M Freeman, Luke I Szweda, Holly Van Remmen, William E Sonntag
OBJECTIVE: A decline in mitochondrial function and biogenesis as well as increased reactive oxygen species (ROS) are important determinants of aging. With advancing age, there is a concomitant reduction in circulating levels of insulin-like growth factor-1 (IGF-1) that is closely associated with neuronal aging and neurodegeneration. In this study, we investigated the effect of the decline in IGF-1 signaling with age on astrocyte mitochondrial metabolism and astrocyte function and its association with learning and memory...
February 1, 2018: Molecular Metabolism
https://www.readbyqxmd.com/read/29459250/adipose-specific-disruption-of-seipin-causes-early-onset-generalised-lipodystrophy-and-altered-fuel-utilisation-without-severe-metabolic-disease
#9
George D Mcilroy, Karla Suchacki, Anke J Roelofs, Wulin Yang, Yanyun Fu, Bo Bai, Robert J Wallace, Cosimo De Bari, William P Cawthorn, Weiping Han, Mirela Delibegović, Justin J Rochford
OBJECTIVE: Mutations to the BSCL2 gene disrupt the protein seipin and cause the most severe form of congenital generalised lipodystrophy (CGL). Affected individuals exhibit a near complete loss of white adipose tissue (WAT) and suffer from metabolic disease. Seipin is critical for adipocyte development in culture and mice with germline disruption to Bscl2 recapitulate the effects of BSCL2 disruption in humans. Here we examined whether loss of Bscl2 specifically in developing adipocytes in vivo is sufficient to prevent adipose tissue development and cause all features observed with congenital BSCL2 disruption...
January 31, 2018: Molecular Metabolism
https://www.readbyqxmd.com/read/29454579/nucleus-accumbens-inflammation-mediates-anxiodepressive-behavior-and-compulsive-sucrose-seeking-elicited-by-saturated-dietary-fat
#10
Léa Décarie-Spain, Sandeep Sharma, Cécile Hryhorczuk, Victor Issa Garcia, Philip A Barker, Nathalie Arbour, Thierry Alquier, Stephanie Fulton
OBJECTIVE: The incidence of depression is significantly compounded by obesity. Obesity arising from excessive intake of high-fat food provokes anxiodepressive behavior and elicits molecular adaptations in the nucleus accumbens (NAc), a region well-implicated in the hedonic deficits associated with depression and in the control of food-motivated behavior. To determine the etiology of diet-induced depression, we studied the impact of different dietary lipids on anxiodepressive behavior and metabolic and immune outcomes and the contribution of NAc immune activity...
January 31, 2018: Molecular Metabolism
https://www.readbyqxmd.com/read/29449181/roux-en-y-gastric-bypass-hypoglycemia-resolves-with-gastric-feeding-or-reversal-confirming-a-non-pancreatic-etiology
#11
Dawn Belt Davis, Jad Khoraki, Martynas Ziemelis, Sirinart Sirinvaravong, Jee Young Han, Guilherme M Campos
OBJECTIVE: Postprandial hypoglycemia is an infrequent but disabling complication of Roux-en-Y gastric bypass (RYGB) surgery. Controversy still exists as to whether the postprandial hyperinsulinemia observed is due to inherent changes in pancreatic β-cell mass or function or to reversible alterations caused by RYGB anatomy. We aimed to determine if gastric feeding or reversal of RYGB would normalize postprandial glucose and hormone excursions in patients with symptomatic hypoglycemia...
January 31, 2018: Molecular Metabolism
https://www.readbyqxmd.com/read/29428595/galanin-enhances-systemic-glucose-metabolism-through-enteric-nitric-oxide-synthase-expressed-neurons
#12
Anne Abot, Alexandre Lucas, Tereza Bautzova, Arnaud Bessac, Audren Fournel, Sophie Le-Gonidec, Philippe Valet, Cédric Moro, Patrice D Cani, Claude Knauf
OBJECTIVE: Decreasing duodenal contraction is now considered as a major focus for the treatment of type 2 diabetes. Therefore, identifying bioactive molecules able to target the enteric nervous system, which controls the motility of intestinal smooth muscle cells, represents a new therapeutic avenue. For this reason, we chose to study the impact of oral galanin on this system in diabetic mice. METHODS: Enteric neurotransmission, duodenal contraction, glucose absorption, modification of gut-brain axis, and glucose metabolism (glucose tolerance, insulinemia, glucose entry in tissue, hepatic glucose metabolism) were assessed...
January 31, 2018: Molecular Metabolism
https://www.readbyqxmd.com/read/29402588/talk-1-reduces-delta-cell-endoplasmic-reticulum-and-cytoplasmic-calcium-levels-limiting-somatostatin-secretion
#13
Nicholas C Vierra, Matthew T Dickerson, Kelli L Jordan, Prasanna K Dadi, Ketaki A Kadare, Molly K Altman, Sarah C Milian, David A Jacobson
OBJECTIVE: Single-cell RNA sequencing studies have revealed that the type-2 diabetes associated two-pore domain K+ (K2P) channel TALK-1 is abundantly expressed in somatostatin-secreting δ-cells. However, a physiological role for TALK-1 in δ-cells remains unknown. We previously determined that in β-cells, K+ flux through endoplasmic reticulum (ER)-localized TALK-1 channels enhances ER Ca2+ leak, modulating Ca2+ handling and insulin secretion. As glucose amplification of islet somatostatin release relies on Ca2+-induced Ca2+ release (CICR) from the δ-cell ER, we investigated whether TALK-1 modulates δ-cell Ca2+ handling and somatostatin secretion...
January 31, 2018: Molecular Metabolism
https://www.readbyqxmd.com/read/29398618/a-role-for-long-chain-acyl-coa-synthetase-4-acsl4-in-diet-induced-phospholipid-remodeling-and-obesity-associated-adipocyte-dysfunction
#14
Elizabeth A Killion, Andrew R Reeves, Mahmoud A El Azzouny, Qing-Wu Yan, Defne Surujon, John D Griffin, Thomas A Bowman, Chunyan Wang, Nirupa R Matthan, Eric L Klett, Dong Kong, John W Newman, Xianlin Han, Mi-Jeong Lee, Rosalind A Coleman, Andrew S Greenberg
OBJECTIVE: Regulation of fatty acid (FA) metabolism is central to adipocyte dysfunction during diet-induced obesity (DIO). Long-chain acyl-CoA synthetase-4 (ACSL4) has been hypothesized to modulate the metabolic fates of polyunsaturated FA (PUFA), including arachidonic acid (AA), but the in vivo actions of ACSL4 are unknown. The purpose of our studies was to determine the in vivo role of adipocyte ACSL4 in regulating obesity-associated adipocyte dysfunction. METHODS: We developed a novel mouse model with adipocyte-specific ablation of ACSL4 (Ad-KO) using loxP Cre recombinase technology...
January 31, 2018: Molecular Metabolism
https://www.readbyqxmd.com/read/29397344/metabolic-intermediates-cellular-messengers-talking-to-chromatin-modifiers
#15
REVIEW
Anna Nieborak, Robert Schneider
BACKGROUND: To maintain homeostasis, cells need to coordinate the expression of their genes. Epigenetic mechanisms controlling transcription activation and repression include DNA methylation and post-translational modifications of histones, which can affect the architecture of chromatin and/or create 'docking platforms' for multiple binding proteins. These modifications can be dynamically set and removed by various enzymes that depend on the availability of key metabolites derived from different intracellular pathways...
January 31, 2018: Molecular Metabolism
https://www.readbyqxmd.com/read/29396371/genome-wide-analysis-of-pdx1-target-genes-in-human-pancreatic-progenitors
#16
Xianming Wang, Michael Sterr, Ingo Burtscher, Shen Chen, Anja Hieronimus, Fausto Machicao, Harald Staiger, Hans-Ulrich Häring, Gabriele Lederer, Thomas Meitinger, Filippo M Cernilogar, Gunnar Schotta, Martin Irmler, Johannes Beckers, Martin Hrabě de Angelis, Michael Ray, Christopher V E Wright, Mostafa Bakhti, Heiko Lickert
OBJECTIVE: Homozygous loss-of-function mutations in the gene coding for the homeobox transcription factor (TF) PDX1 leads to pancreatic agenesis, whereas heterozygous mutations can cause Maturity-Onset Diabetes of the Young 4 (MODY4). Although the function of Pdx1 is well studied in pre-clinical models during insulin-producing β-cell development and homeostasis, it remains elusive how this TF controls human pancreas development by regulating a downstream transcriptional program. Also, comparative studies of PDX1 binding patterns in pancreatic progenitors and adult β-cells have not been conducted so far...
January 30, 2018: Molecular Metabolism
https://www.readbyqxmd.com/read/29396373/circular-rnas-as-novel-regulators-of-%C3%AE-cell-functions-in-normal-and-disease-conditions
#17
Lisa Stoll, Jonathan Sobel, Adriana Rodriguez-Trejo, Claudiane Guay, Kailun Lee, Morten Trillingsgaard Venø, Jørgen Kjems, D Ross Laybutt, Romano Regazzi
OBJECTIVE: There is strong evidence for an involvement of different classes of non-coding RNAs, including microRNAs and long non-coding RNAs, in the regulation of β-cell activities and in diabetes development. Circular RNAs were recently discovered to constitute a substantial fraction of the mammalian transcriptome but the contribution of these non-coding RNAs in physiological and disease processes remains largely unknown. The goal of this study was to identify the circular RNAs expressed in pancreatic islets and to elucidate their possible role in the control of β-cells functions...
January 29, 2018: Molecular Metabolism
https://www.readbyqxmd.com/read/29396372/ghrelin-mediates-exercise-endurance-and-the-feeding-response-post-exercise
#18
Bharath K Mani, Carlos M Castorena, Sherri Osborne-Lawrence, Prasanna Vijayaraghavan, Nathan P Metzger, Joel K Elmquist, Jeffrey M Zigman
OBJECTIVE: Exercise training has several well-established health benefits, including many related to body weight, appetite control, and blood glucose homeostasis. However, the molecular mechanisms and, in particular, the hormonal systems that mediate and integrate these beneficial effects are poorly understood. In the current study, we aimed to investigate the role of the hormone ghrelin and its receptor, the growth hormone secretagogue receptor (GHSR; ghrelin receptor), in mediating the effects of exercise on food intake and blood glucose following exercise as well as in regulating exercise endurance capacity...
January 27, 2018: Molecular Metabolism
https://www.readbyqxmd.com/read/29396368/liver-specific-rescuing-of-ceacam1-reverses-endothelial-and-cardiovascular-abnormalities-in-male-mice-with-null-deletion-of-ceacam1-gene
#19
Lucia Russo, Harrison T Muturi, Hilda E Ghadieh, Alexander M Wisniewski, Eric E Morgan, Syed S Quadri, Gavin P Landesberg, Helmy M Siragy, Guillermo Vazquez, Rosario Scalia, Rajesh Gupta, Sonia M Najjar
OBJECTIVE: Mice with global null mutation of Ceacam1 (Cc1-/-), display impairment of insulin clearance that causes hyperinsulinemia followed by insulin resistance, elevated hepatic de novo lipogenesis, and visceral obesity. In addition, they manifest abnormal vascular permeability and elevated blood pressure. Liver-specific rescuing of Ceacam1 reversed all of the metabolic abnormalities in Cc1-/-liver+ mice. The current study examined whether Cc1-/- male mice develop endothelial and cardiac dysfunction and whether this relates to the metabolic abnormalities caused by defective insulin extraction...
January 26, 2018: Molecular Metabolism
https://www.readbyqxmd.com/read/29396375/corrigendum-to-metabolic-adaptation-to-intermittent-fasting-is-independent-of-peroxisome-proliferator-activated-receptor-alpha-mol-metab-7-2018-80-89
#20
Guolin Li, Chad N Brocker, Tingting Yan, Cen Xie, Kristopher W Krausz, Rong Xiang, Frank J Gonzalez
No abstract text is available yet for this article.
January 23, 2018: Molecular Metabolism
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