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Molecular Metabolism

Katarzyna Malenczyk, Edit Szodorai, Robert Schnell, Gert Lubec, Gábor Szabó, Tomas Hökfelt, Tibor Harkany
OBJECTIVE: Specification of endocrine cell lineages in the developing pancreas relies on extrinsic signals from non-pancreatic tissues, which initiate a cell-autonomous sequence of transcription factor activation and repression switches. The steps in this pathway share reliance on activity-dependent Ca2+ signals. However, the mechanisms by which phasic Ca2+ surges become converted into a dynamic, cell-state-specific and physiologically meaningful code made up by transcription factors constellations remain essentially unknown...
June 5, 2018: Molecular Metabolism
Balyssa B Bell, Shannon M Harlan, Donald A Morgan, Deng-Fu Guo, Huxing Cui, Kamal Rahmouni
No abstract text is available yet for this article.
June 4, 2018: Molecular Metabolism
Maureen Gannon, Rohit N Kulkarni, Hubert M Tse, Franck Mauvais-Jarvis
BACKGROUND: The sex of an individual affects glucose homeostasis and the pathophysiology, incidence, and prevalence of diabetes as well as the response to therapy. SCOPE OF THE REVIEW: This review focuses on clinical and experimental sex differences in islet cell biology and dysfunction during development and in adulthood in human and animal models. We discuss sex differences in β-cell and α-cell function, heterogeneity, and dysfunction. We cover sex differences in communication between gonads and islets and islet-cell immune interactions...
May 30, 2018: Molecular Metabolism
Tzu-Wen L Cross, Kazuyuki Kasahara, Federico E Rey
BACKGROUND: Sex is one of the most powerful modifiers of disease development. Clear sexual dimorphism exists in cardiometabolic health susceptibility, likely due to differences in sex steroid hormones. Changes in the gut microbiome have been linked with the development of obesity, type 2 diabetes, and atherosclerosis; however, the impact of microbes in sex-biased cardiometabolic disorders remains unclear. The gut microbiome is critical for maintaining a normal estrous cycle, testosterone levels, and reproductive function...
May 30, 2018: Molecular Metabolism
Yong Xu, Miguel López
BACKGROUND: Estrogenic actions in the brain prevent obesity. Better understanding of the underlying mechanisms may facilitate development of new obesity therapies. SCOPE OF REVIEW: This review focuses on the critical brain regions that mediate effects of estrogens on food intake and/or energy expenditure, the molecular signals that are involved, and the functional interactions between brain estrogens and other signals modulating metabolism. Body weight regulation by estrogens in male brains will also be discussed...
May 23, 2018: Molecular Metabolism
Florian Kahles, Ana Liberman, Constantin Halim, Matthias Rau, Julia Möllmann, Robert Werner Mertens, Marcia Rückbeil, Irmgard Diepolder, Benedikt Walla, Sebastian Diebold, Mathias Burgmaier, Corinna Lebherz, Nikolaus Marx, Michael Lehrke
OBJECTIVE: The incretin hormones GLP-1 (glucagon-like peptide-1) and GIP (glucose-dependent insulinotropic peptide) are secreted by the gut after food intake leading to pancreatic insulin secretion and glucose lowering. Beyond its role in glucose control, GLP-1 was found in mice and men to beneficially modulate the process of atherosclerosis, which has been linked to improved cardiovascular outcome of patients with diabetes at high cardiovascular risk treated with GLP-1 receptor agonists...
May 23, 2018: Molecular Metabolism
Lin Jia, Xiuli Chang, Shuwen Qian, Chen Liu, Caleb C Lord, Newaz Ahmed, Charlotte E Lee, Syann Lee, Laurent Gautron, Mack C Mitchell, Jay D Horton, Philipp E Scherer, Joel K Elmquist
OBJECTIVE: Recent studies have suggested a critical role for toll-like receptor 4 (TLR4) in the development of alcoholic liver disease. As TLR4 is widely expressed throughout the body, it is unclear which TLR4-expressing cell types contribute to alcohol-induced liver damage. METHODS: We selectively ablated TLR4 in hepatocytes and myeloid cells. Male mice were fed a liquid diet containing either 5% alcohol or pair-fed a control diet for 4 weeks to examine chronic alcohol intake-induced liver damage and inflammation...
May 23, 2018: Molecular Metabolism
Markus Mühlemann, Daniela Zdzieblo, Alexandra Friedrich, Constantin Berger, Christoph Otto, Heike Walles, Hermann Koepsell, Marco Metzger
OBJECTIVES: Glycemic control by medical treatment represents one therapeutic strategy for diabetic patients. The Na+-d-glucose cotransporter 1 (SGLT1) is currently of high interest in this context. SGLT1 is known to mediate glucose absorption and incretin secretion in the small intestine. Recently, inhibition of SGLT1 function was shown to improve postprandial hyperglycemia. In view of the lately demonstrated SGLT1 expression in pancreatic islets, we investigated if loss of SGLT1 affects islet morphology and function...
May 23, 2018: Molecular Metabolism
Danielle J Sanchez, David J Steger, Nicolas Skuli, Ankita Bansal, M Celeste Simon
OBJECTIVE: Clear cell renal cell carcinoma (ccRCC) is a subtype of kidney cancer defined by robust lipid accumulation, which prior studies have indicated plays an important role in tumor progression. We hypothesized that the peroxisome proliferator-activated receptor gamma (PPARγ), detected in both ccRCC tumors and cell lines, promotes lipid storage in ccRCC and contributes to tumorigenesis in this setting. PPARγ transcriptionally regulates a number of genes involved in lipid and glucose metabolism in adipocytes, yet its role in ccRCC has not been described...
May 21, 2018: Molecular Metabolism
Ilaria Panzeri, John Andrew Pospisilik
BACKGROUND: The alarming rise of obesity and its associated comorbidities represents a medical burden and a major global health and economic issue. Understanding etiological mechanisms underpinning susceptibility and therapeutic response is of primary importance. Obesity, diabetes, and metabolic diseases are complex trait disorders with only partial genetic heritability, indicating important roles for environmental programing and epigenetic effects. SCOPE OF THE REVIEW: We will highlight some of the reasons for the scarce predictability of metabolic diseases...
May 18, 2018: Molecular Metabolism
Brian T Palmisano, Lin Zhu, Robert H Eckel, John M Stafford
BACKGROUND: Endogenous sex hormones are important for metabolic health in men and women. Before menopause, women are protected from atherosclerotic cardiovascular disease (ASCVD) relative to men. Women have fewer cardiovascular complications of obesity compared to men with obesity. Endogenous estrogens have been proposed as a mechanism that lessens ASCVD risk, as risk of glucose and lipid abnormalities increases when endogenous estrogens decline with menopause. While baseline risk is higher in males than females, endogenously produced androgens are also protective against fatty liver, diabetes and ASCVD, as risk goes up with androgen deprivation and with the decline in androgens with age...
May 16, 2018: Molecular Metabolism
Pierre Gourdy, Maeva Guillaume, Coralie Fontaine, Marine Adlanmerini, Alexandra Montagner, Henrik Laurell, Françoise Lenfant, Jean-François Arnal
BACKGROUND: In addition to their crucial role in reproduction, estrogens are key regulators of energy and glucose homeostasis and they also exert several cardiovascular protective effects. These beneficial actions are mainly mediated by estrogen receptor alpha (ERα), which is widely expressed in metabolic and vascular tissues. As a member of the nuclear receptor superfamily, ERα was primarily considered as a transcription factor that controls gene expression through the activation of its two activation functions (ERαAF-1 and ERαAF-2)...
May 16, 2018: Molecular Metabolism
Amandine Girousse, Samuel Virtue, Dan Hart, Antonio Vidal-Puig, Peter R Murgatroyd, Etienne Mouisel, Coralie Sengenès, David B Savage
OBJECTIVE: Surplus dietary fat cannot be converted into other macronutrient forms or excreted, so has to be stored or oxidized. Healthy mammals store excess energy in the form of triacylgycerol (TAG) in lipid droplets within adipocytes rather than oxidizing it, and thus ultimately gain weight. The 'overflow hypothesis' posits that the capacity to increase the size and number of adipocytes is finite and that when this limit is exceeded, fat accumulates in ectopic sites and leads to metabolic disease...
May 16, 2018: Molecular Metabolism
Louise Montagne, Mehdi Derhourhi, Amélie Piton, Bénédicte Toussaint, Emmanuelle Durand, Emmanuel Vaillant, Dorothée Thuillier, Stefan Gaget, Franck De Graeve, Iandry Rabearivelo, Amélie Lansiaux, Bruno Lenne, Sylvie Sukno, Rachel Desailloud, Miriam Cnop, Ramona Nicolescu, Lior Cohen, Jean-François Zagury, Mélanie Amouyal, Jacques Weill, Jean Muller, Olivier Sand, Bruno Delobel, Philippe Froguel, Amélie Bonnefond
OBJECTIVE: The molecular diagnosis of extreme forms of obesity, in which accurate detection of both copy number variations (CNVs) and point mutations, is crucial for an optimal care of the patients and genetic counseling for their families. Whole-exome sequencing (WES) has benefited considerably this molecular diagnosis, but its poor ability to detect CNVs remains a major limitation. We aimed to develop a method (CoDE-seq) enabling the accurate detection of both CNVs and point mutations in one step...
May 16, 2018: Molecular Metabolism
Wolfgang Langhans, Roger Adan, Myrtha Arnold, William A Banks, J Patrick Card, Megan J Dailey, Derek Daniels, Annette D de Kloet, Guillaume de Lartigue, Suzanne Dickson, Shahana Fedele, Harvey J Grill, John-Olov Jansson, Sharon Kaufman, Grant Kolar, Eric Krause, Shin J Lee, Christelle Le Foll, Barry E Levin, Thomas A Lutz, Abdelhak Mansouri, Timothy H Moran, Gustavo Pacheco-López, Deepti Ramachandran, Helen Raybould, Linda Rinaman, Willis K Samson, Graciela Sanchez-Watts, Randy J Seeley, Karolina P Skibicka, Dana Small, Alan C Spector, Kellie L Tamashiro, Brian Templeton, Stefan Trapp, Patrick Tso, Alan G Watts, Nadja Weissfeld, Diana Williams, Christian Wolfrum, Gina Yosten, Stephen C Woods
No abstract text is available yet for this article.
May 12, 2018: Molecular Metabolism
Archita Agrawal, Sebastian Parlee, Diego Perez-Tilve, Pengyun Li, Jia Pan, Piotr A Mroz, Ann Maria Kruse Hansen, Birgitte Andersen, Brian Finan, Alexei Kharitonenkov, Richard D DiMarchi
OBJECTIVE: To signal, FGF19 and FGF21 require co-receptor βKlotho (KLB) to act in concert with FGF receptors, and yet there is appreciable variance in the C-terminal sequences of these two novel metabolic hormones where binding is believed to be primary. We seek to determine the functional consequences for these amino acid differences and determine whether such information can be used to design high potency antagonists and agonists. METHODS: We employed a functional in vitro assay to identify C-terminal protein fragments capable of fully blocking KLB-mediated FGF19 and 21 receptor signaling...
May 11, 2018: Molecular Metabolism
Marc Schneeberger, Keith Tan, Alexander R Nectow, Luca Parolari, Caner Caglar, Estefania Azevedo, Zhiying Li, Ana Domingos, Jeffrey M Friedman
OBJECTIVES: Melanin-concentrating hormone (MCH) neurons in the lateral hypothalamus (LH) regulate food intake and body weight, glucose metabolism and convey the reward value of sucrose. In this report, we set out to establish the respective roles of MCH and conventional neurotransmitters in these neurons. METHODS: MCH neurons were profiled using Cre-dependent molecular profiling technologies (vTRAP). MCHCre mice crossed to Vglut2fl/fl mice or to DTRfl/fl were used to identify the role of glutamate in MCH neurons...
May 8, 2018: Molecular Metabolism
N J Lee, N Ali, L Zhang, Y Qi, I Clarke, R F Enriquez, M Brzozowska, I C Lee, M J Rogers, D R Laybutt, J R Center, P A Baldock, H Herzog
OBJECTIVE: The skeleton, which is strongly controlled by endocrine factors, has recently been shown to also play an active endocrine role itself, specifically influencing energy metabolism. However, much less is known about this role. Therefore, we sought to identify novel endocrine factors involved in the regulation of both bone mass and whole-body glucose homeostasis. METHODS: We used transcriptomic and proteomic analysis of Y1 receptor deficient osteoblasts combined with the generation of a novel osteoglycin deficient mouse model and performed comprehensive in vivo phenotype profiling, combined with osteoglycin administration in wildtype mice and human studies...
May 8, 2018: Molecular Metabolism
Lena Wischhof, Anna Gioran, Dagmar Sonntag-Bensch, Antonia Piazzesi, Miriam Stork, Pierluigi Nicotera, Daniele Bano
OBJECTIVE: Mutations in the AIFM1 gene have been identified in recessive X-linked mitochondrial diseases. Functional and molecular consequences of these pathogenic AIFM1 mutations have been poorly studied in vivo. METHODS/RESULTS: Here we provide evidence that the disease-associated apoptosis-inducing factor (AIF) deletion arginine 201 (R200 in rodents) causes pathology in knockin mice. Within a few months, posttranslational loss of the mutant AIF protein induces severe myopathy associated with a lower number of cytochrome c oxidase-positive muscle fibers...
May 8, 2018: Molecular Metabolism
Laura Dearden, Sebastien G Bouret, Susan E Ozanne
BACKGROUND: The early life environment experienced by an individual in utero and during the neonatal period is a major factor in shaping later life disease risk-including susceptibility to develop obesity, diabetes, and cardiovascular disease. The incidence of metabolic disease is different between males and females. How the early life environment may underlie these sex differences is an area of active investigation. SCOPE OF REVIEW: The purpose of this review is to summarize our current understanding of how the early life environment influences metabolic disease risk in a sex specific manner...
April 30, 2018: Molecular Metabolism
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