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Trends in Endocrinology and Metabolism: TEM

Wen-Bin Alfred Chng, Ville Hietakangas, Bruno Lemaitre
Sugars are important energy sources, but high sugar intake poses a metabolic challenge and leads to diseases. Drosophila melanogaster is a generalist fruit breeder that encounters high levels of dietary sugars in its natural habitat. Consequently, Drosophila displays adaptive responses to dietary sugars, including highly conserved and unique metabolic adaptations not described in mammals. Carbohydrate homeostasis is maintained by a network comprising intracellular energy sensors, transcriptional regulators, and hormonal and neuronal mechanisms that together coordinate animal behavior, gut function, and metabolic flux...
December 3, 2016: Trends in Endocrinology and Metabolism: TEM
Nathan J Pavlos, Peter A Friedman
Emerging findings disclose unexpected components of G protein-coupled receptor (GPCR) signaling and cell biology. Select GPCRs exhibit classical signaling, that is restricted to cell membranes, as well as newly described persistent signaling that depends on internalization of the GPCR bound to β-arrestins. Termination of non-canonical endosomal signaling requires intraluminal acidification and sophisticated protein trafficking machineries. Recent studies reveal the structural determinants of the trafficking chaperones...
November 23, 2016: Trends in Endocrinology and Metabolism: TEM
Carlos Sebastián, Raul Mostoslavsky
Glucose-derived acetyl-CoA levels directly impact histone acetylation, linking the energetic status of the cell to its epigenome. Two recent reports showed that other carbon sources can contribute to the acetyl-CoA pool used for histone acetylation, highlighting the metabolic plasticity that allows cells to respond to nutrient availability.
November 15, 2016: Trends in Endocrinology and Metabolism: TEM
Luisa Tasselli, Wei Zheng, Katrin F Chua
SIRT6, a member of the Sirtuin family of NAD(+)-dependent enzymes, has established roles in chromatin signaling and genome maintenance. Through these functions, SIRT6 protects against aging-associated pathologies including metabolic disease and cancer, and can promote longevity in mice. Research from the past few years revealed that SIRT6 is a complex enzyme with multiple substrates and catalytic activities, and uncovered novel SIRT6 functions in the maintenance of organismal health span. Here, we review these new discoveries and models of SIRT6 biology in four areas: heterochromatin stabilization and silencing; stem cell biology; cancer initiation and progression; and regulation of metabolic homeostasis...
November 8, 2016: Trends in Endocrinology and Metabolism: TEM
Clara E Cho, Marie A Caudill
Trimethylamine-N-oxide (TMAO), a gut-derived metabolite, has recently emerged as a candidate risk factor for cardiovascular disease and other adverse health outcomes. However, the relation between TMAO and chronic disease can be confounded by several factors, including kidney function, the gut microbiome, and flavin-containing monooxygenase 3 (FMO3) genotype. Thus, whether TMAO is a causative agent in human disease development and progression, or simply a marker of an underlying pathology, remains inconclusive...
November 4, 2016: Trends in Endocrinology and Metabolism: TEM
Leon G Straub, Christian Wolfrum
The histone lysine-specific demethylase 1 (LSD1) is a new and important player in the regulation of brown fat identity and function. In a recent Cell Reports article, Duteil et al. show that LSD1 exerts its effects via regulation of specific histone marks as well as through association with co-repressor complexes.
November 1, 2016: Trends in Endocrinology and Metabolism: TEM
Isabel Huang-Doran, Chen-Yu Zhang, Antonio Vidal-Puig
Metabolic homeostasis emerges from the complex, multidirectional crosstalk between key metabolic tissues including adipose tissue, liver, and skeletal muscle. This crosstalk, traditionally mediated by hormones and metabolites, becomes dysregulated in human diseases such as obesity and diabetes. Extracellular vesicles (EVs; including exosomes) are circulating, cell-derived nanoparticles containing proteins and nucleic acids that interact with and modify local and distant cellular targets. Accumulating evidence, reviewed herein, supports a role for extracellular vesicles in obesity-associated metabolic disturbance, particularly the local and systemic inflammation characteristic of adipose and hepatic stress...
October 31, 2016: Trends in Endocrinology and Metabolism: TEM
Giovanna Muscogiuri, Ralph A DeFronzo, Amalia Gastaldelli, Jens J Holst
Glucagon-like peptide-1 (GLP-1) is released in response to meals and exerts important roles in the maintenance of normal glucose homeostasis. GLP-1 is also important in the regulation of neurologic and cognitive functions. These actions are mediated via neurons in the nucleus of the solitary tract that project to multiple regions expressing GLP-1 receptors (GLP-1Rs). Treatment with GLP-1R agonists (GLP-1-RAs) reduces ischemia-induced hyperactivity, oxidative stress, neuronal damage and apoptosis, cerebral infarct volume, and neurologic damage, after cerebral ischemia, in experimental models...
October 27, 2016: Trends in Endocrinology and Metabolism: TEM
Claudio Franceschi, Paolo Garagnani, Giovanni Vitale, Miriam Capri, Stefano Salvioli
'Inflammaging' refers to the chronic, low-grade inflammation that characterizes aging. Inflammaging is macrophage centered, involves several tissues and organs, including the gut microbiota, and is characterized by a complex balance between pro- and anti-inflammatory responses. Based on literature data, we argue that the major source of inflammatory stimuli is represented by endogenous/self, misplaced, or altered molecules resulting from damaged and/or dead cells and organelles (cell debris), recognized by receptors of the innate immune system...
October 24, 2016: Trends in Endocrinology and Metabolism: TEM
Ruth Ganss
Current therapies for pregnancy-related hypertension and its complications remain inadequate, although an increasing role for maternal susceptibility is becoming evident. Systemic vascular dysfunction in response to imbalances in angiogenic, inflammatory, and constricting factors is implicated in the pathogenesis of gestational hypertension, and growing evidence now links these factors with maternal metabolism. In particular, the crucial role of peroxisome proliferator-activated receptors (PPARs) in maternal vascular adaptation provides further insights into how obesity and gestational diabetes may be linked to pregnancy-induced hypertension and preeclampsia...
October 24, 2016: Trends in Endocrinology and Metabolism: TEM
Amy Karol Walker
Fatty liver is a complex disease often accompanying metabolic syndrome and Type 2 diabetes mellitus (T2DM). Hepatosteatosis may have roots in multiple metabolic abnormalities. However, metabolic dysfunction in the 1-carbon cycle (1CC), which produces the methyl donor S-adenosylmethionine (SAM) and phosphatidylcholine (PC), induces hepatic lipogenesis in model systems. Human diseases where 1CC or PC synthesis is disrupted, such as alcoholism, congenital lipodystrophy, or cystic fibrosis, often present with fatty liver...
October 24, 2016: Trends in Endocrinology and Metabolism: TEM
Audrey Sambeat, Olga Gulyaeva, Jon Dempersmier, Hei Sook Sul
In contrast to white adipose tissue (WAT), which stores energy in the form of triglycerides, brown adipose tissue (BAT) dissipates energy by producing heat to maintain body temperature by burning glucose and fatty acids in a process called adaptive thermogenesis. The presence of an inducible thermogenic adipose tissue, and its beneficial effects for maintaining body weight and glucose and lipid homeostasis, has raised intense interest in understanding the regulation of thermogenesis. Elucidating the regulatory mechanisms underlying the thermogenic adipose program may provide excellent targets for therapeutics against obesity and diabetes...
September 27, 2016: Trends in Endocrinology and Metabolism: TEM
Pierre Theurey, Jennifer Rieusset
Metabolic diseases are associated with nutrient excess and metabolic inflexibility. Mitochondria and endoplasmic reticulum are important organelles and nutrient sensors, and their dysfunction has been extensively and independently implicated in metabolic diseases. Both organelles interact at sites known as mitochondria-associated membranes (MAMs), in order to exchange metabolites and calcium. Recent evidence indicates that MAM could be a hub of hepatic insulin signaling and nutrient sensing. In this review, we discuss the roles organelle function and communication play in the cell's adaptation to nutrient availability, in both physiology and metabolic diseases...
September 23, 2016: Trends in Endocrinology and Metabolism: TEM
Maria Conte, Claudio Franceschi, Marco Sandri, Stefano Salvioli
Perilipin 2 (Plin2), a protein associated with the metabolism of intracellular lipid droplets (LDs), has long been considered only for its role in lipid storage. However, the manipulation of its expression affects the severity of a variety of metabolic and age-related diseases, such as fatty liver, insulin resistance and type 2 diabetes (T2D), cardiovascular disease, atherosclerosis, sarcopenia, and cancer, suggesting that this protein may play a role in these pathological conditions. In particular, its downregulation in mice prevents or mitigates some of the above mentioned diseases...
September 19, 2016: Trends in Endocrinology and Metabolism: TEM
Joanne Boldison, F Susan Wong
The autoimmune destruction of the pancreatic islet β cells is due to a targeted lymphocyte attack. Different T cell subsets communicate with each other and with the insulin-producing β cells in this process, with evidence not only of damage to the tissue cells but also of lymphocyte regulation. Here we explore the various components of the immune response as well as the cellular interactions that are involved in causing or reducing immune damage to the β cells. We consider these in the light of the possibility that understanding them may help us identify therapeutic targets to reduce the damage and destruction leading to type 1 diabetes...
September 19, 2016: Trends in Endocrinology and Metabolism: TEM
Meghna Pant, Naresh C Bal, Muthu Periasamy
Skeletal muscle constitutes ∼40% of body mass and has the capacity to play a major role as thermogenic, metabolic, and endocrine organ. In addition to shivering, muscle also contributes to nonshivering thermogenesis via futile sarcoplasmic/endoplasmic reticulum Ca(2+) ATPase (SERCA) activity. Sarcolipin (SLN), a regulator of SERCA activity in muscle, plays an important role in regulating muscle thermogenesis and metabolism. Uncoupling of SERCA by SLN increases ATP hydrolysis and heat production, and contributes to temperature homeostasis...
September 13, 2016: Trends in Endocrinology and Metabolism: TEM
Claire L Donohoe, Joanne Lysaght, Jacintha O'Sullivan, John V Reynolds
There is compelling epidemiological evidence linking obesity to many tumours; however, the molecular mechanisms fuelling this association are not clearly understood. Emerging evidence links changes in the tumour microenvironment with the obese state, and murine and human studies highlight the relevance of adipose stromal cells (ASCs), including immune cells, both at remote fat depots, such as the omentum, as well as in peritumoural tissue. These obesity-associated changes have been implicated in several hallmarks of cancer, including the chronic inflammatory state and associated cell signalling, epithelial-to-mesenchymal transition (EMT), tumour-related fibrosis, angiogenesis, and genomic instability...
September 12, 2016: Trends in Endocrinology and Metabolism: TEM
Franck Mauvais-Jarvis
The gonads have long been considered endocrine glands, producing sex steroids such as estrogens, androgens, and progesterone (P4) for the sole purpose of sexual differentiation, puberty, and reproduction. Reproduction and energy metabolism are tightly linked, however, and gonadal steroids play an important role in sex-specific aspects of energy metabolism in various physiological conditions. In that respect, gonadal steroids also influence the secretion of insulin in a sex-specific manner. This review presents a perspective on the physiological roles of estrogens, androgens, and P4 via their receptors in pancreatic β cells in the gender-specific tuning of insulin secretion...
December 2016: Trends in Endocrinology and Metabolism: TEM
Timothy W Hand, Ivan Vujkovic-Cvijin, Vanessa K Ridaura, Yasmine Belkaid
Chronic inflammatory diseases (CIDs) are the most important causes of mortality in the world today and are on the rise. We now know that immune-driven inflammation is critical in the etiology of these diseases, though the environmental triggers and cellular mechanisms that lead to their development are still mysterious. Many CIDs are associated with significant shifts in the microbiota toward inflammatory configurations, which can affect the host both by inducing local and systemic inflammation and by alterations in microbiota-derived metabolites...
December 2016: Trends in Endocrinology and Metabolism: TEM
Christopher Lipina, Harinder S Hundal
Regulated in development and DNA damage response 1 (REDD1) has been functionally linked to the control of diverse cellular processes due, at least in part, to its ability to repress mammalian or mechanistic Target of Rapamycin (mTOR) Complex-1 (mTORC1), a key protein complex controlled by hormonal and nutrient cues. Notably, emerging evidence suggests that REDD1 also regulates several pathways involved in modulating energy balance and metabolism. Herein, we discuss evidence implicating REDD1 as a key modulator of insulin action and metabolic function, including its potential contribution to mitochondrial biology and pancreatic islet function...
December 2016: Trends in Endocrinology and Metabolism: TEM
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