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https://www.readbyqxmd.com/read/27913603/the-tumor-suppressor-flcn-mediates-an-alternate-mtor-pathway-to-regulate-browning-of-adipose-tissue
#1
Shogo Wada, Michael Neinast, Cholsoon Jang, Yasir H Ibrahim, Gina Lee, Apoorva Babu, Jian Li, Atsushi Hoshino, Glenn C Rowe, James Rhee, José A Martina, Rosa Puertollano, John Blenis, Michael Morley, Joseph A Baur, Patrick Seale, Zoltan Arany
Noncanonical mechanistic target of rapamycin (mTOR) pathways remain poorly understood. Mutations in the tumor suppressor folliculin (FLCN) cause Birt-Hogg-Dubé syndrome, a hamartomatous disease marked by mitochondria-rich kidney tumors. FLCN functionally interacts with mTOR and is expressed in most tissues, but its role in fat has not been explored. We show here that FLCN regulates adipose tissue browning via mTOR and the transcription factor TFE3. Adipose-specific deletion of FLCN relieves mTOR-dependent cytoplasmic retention of TFE3, leading to direct induction of the PGC-1 transcriptional coactivators, drivers of mitochondrial biogenesis and the browning program...
December 2, 2016: Genes & Development
https://www.readbyqxmd.com/read/27913573/thyroid-hormones-induce-browning-of-white-fat
#2
Noelia Martinez, José María Moreno-Navarrete, Cristina Contreras, Eva Rial-Pensado, Johan Fernø, Rubén Nogueiras, Carlos Diéguez, José M Fernández-Real, Miguel López
The canonical view about the effect of thyroid hormones (THs) on thermogenesis assumes that the hypothalamus acts merely as a modulator of the sympathetic outflow on brown adipose tissue (BAT). Recent data have challenged that vision by demonstrating that THs act on the ventromedial nucleus of the hypothalamus (VMH) to inhibit AMP-activated protein kinase (AMPK), which regulates the thermogenic program in BAT, leading to increased thermogenesis and weight loss. Current data have shown that in addition to activation of brown fat, the browning of white adipose tissue (WAT) might be also an important thermogenic mechanism...
December 2, 2016: Journal of Endocrinology
https://www.readbyqxmd.com/read/27911598/type-3-deiodinase-role-on-central-thyroid-hormone-action-affects-the-leptin-melanocortin-system-and-circadian-activity
#3
Zhaofei Wu, M Elena Martinez, Donald L St Germain, Arturo Hernandez
The role of thyroid hormones (TH) in the central regulation of energy balance is increasingly appreciated. Mice lacking the type 3 deiodinase (DIO3), which inactivates TH, have decreased circulating TH levels relative to control mice due to defects in the hypothalamic-pituitary-thyroid axis. However, we have shown that the TH status of the adult Dio3(-/-) brain is opposite that of the serum, exhibiting enhanced levels of TH action. Since the brain, specially the hypothalamus, harbors important circuitries that regulate metabolism, we aimed to examine the energy balance phenotype of Dio3(-/-) mice and determine whether it is associated with hypothalamic abnormalities...
December 2, 2016: Endocrinology
https://www.readbyqxmd.com/read/27906714/central-nervous-system-regulation-of-hepatic-lipid-and-lipoprotein-metabolism
#4
Jennifer Taher, Sarah Farr, Khosrow Adeli
PURPOSE OF REVIEW: Hepatic lipid and lipoprotein metabolism is an important determinant of fasting dyslipidemia and the development of fatty liver disease. Although endocrine factors like insulin have known effects on hepatic lipid homeostasis, emerging evidence also supports a regulatory role for the central nervous system (CNS) and neuronal networks. This review summarizes evidence implicating a bidirectional liver-brain axis in maintaining metabolic lipid homeostasis, and discusses clinical implications in insulin-resistant states...
November 30, 2016: Current Opinion in Lipidology
https://www.readbyqxmd.com/read/27901369/involvement-of-endogenous-central-hydrogen-sulfide-h2s-in-hypoxia-induced-hypothermia-in-spontaneously-hypertensive-rats
#5
João Paulo J Sabino, Renato N Soriano, Alberto F Donatti, Rodrigo Restrepo Fernandez, Marcelo Kwiatkoski, Heloísa D C Francescato, Terezila M Coimbra, Luiz G S Branco
Spontaneously hypertensive rats (SHR) display autonomic imbalance and abnormal body temperature (Tb) adjustments. Hydrogen sulfide (H2S) modulates hypoxia-induced hypothermia, but its role in SHR thermoregulation is unknown. We tested the hypothesis that SHR display peculiar thermoregulatory response to hypoxia and that endogenous H2S overproduced in the caudal nucleus of the solitary tract (NTS) of SHR modulates this response. SHR and Wistar rats were microinjected into the fourth ventricle with aminooxyacetate (AOA, H2S-synthezing enzyme inhibitor) or sodium sulfide (Na2S, H2S donor) and exposed to normoxia (21% inspired O2) or hypoxia (10% inspired O2, 30 min)...
September 6, 2016: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/27901032/from-the-past-to-future-from-energy-expenditure-to-energy-intake-to-energy-expenditure
#6
REVIEW
M J Müller, C Geisler
Although most recent research on energy balance focusses on energy intake (EI) there is still need to think about both sides of the energy balance. Current research on energy expenditure (EE) relates to metabolic adaptation to negative energy balance, mitochondrial metabolism associated with aging, obesity and type 2 diabetes mellitus, the role of EE in hunger and appetite control, non-shivering thermogenesis and brown adipose tissue activity, cellular bioenergetics as a target of obesity treatment and the evolutionary and ecological determinants of EE in humans and other primates...
November 30, 2016: European Journal of Clinical Nutrition
https://www.readbyqxmd.com/read/27900258/adipocyte-specific-hypoxia-inducible-gene-2-promotes-fat-deposition-and-diet-induced-insulin-resistance
#7
Marina T DiStefano, Rachel J Roth Flach, Ozlem Senol-Cosar, Laura V Danai, Joseph V Virbasius, Sarah M Nicoloro, Juerg Straubhaar, Sezin Dagdeviren, Martin Wabitsch, Olga T Gupta, Jason K Kim, Michael P Czech
OBJECTIVE: Adipose tissue relies on lipid droplet (LD) proteins in its role as a lipid-storing endocrine organ that controls whole body metabolism. Hypoxia-inducible Gene 2 (Hig2) is a recently identified LD-associated protein in hepatocytes that promotes hepatic lipid storage, but its role in the adipocyte had not been investigated. Here we tested the hypothesis that Hig2 localization to LDs in adipocytes promotes adipose tissue lipid deposition and systemic glucose homeostasis. METHOD: White and brown adipocyte-deficient (Hig2(fl/fl) × Adiponection cre+) and selective brown/beige adipocyte-deficient (Hig2(fl/fl) × Ucp1 cre+) mice were generated to investigate the role of Hig2 in adipose depots...
December 2016: Molecular Metabolism
https://www.readbyqxmd.com/read/27899046/chili-pepper-as-a-body-weight-loss-food
#8
Sharon Varghese, Peter Kubatka, Luis Rodrigo, Katarina Gazdikova, Martin Caprnda, Julia Fedotova, Anthony Zulli, Peter Kruzliak, Dietrich Büsselberg
Chili has culinary as well as medical importance. Studies in humans, using a wide range of doses of chili intake (varying from a single meal to a continuous uptake for up to 12 weeks), concluded that it facilitates weight loss. In regard to this, the main targets of chili are fat metabolism, energy expenditure, and thermogenesis. To induce weight loss, the active substance of chili, capsaicin, activates Transient Receptor Potential Cation Channel sub-family V member 1 (TRPV1) channels) receptors causing an increase in intracellular calcium levels and triggering the sympathetic nervous system...
November 29, 2016: International Journal of Food Sciences and Nutrition
https://www.readbyqxmd.com/read/27895388/acetate-alters-expression-of-genes-involved-in-beige-adipogenesis-in-3t3-l1-cells-and-obese-kk-ay-mice
#9
Satoko Hanatani, Hiroyuki Motoshima, Yuki Takaki, Shuji Kawasaki, Motoyuki Igata, Takeshi Matsumura, Tatsuya Kondo, Takafumi Senokuchi, Norio Ishii, Junji Kawashima, Daisuke Kukidome, Seiya Shimoda, Takeshi Nishikawa, Eiichi Araki
The induction of beige adipogenesis within white adipose tissue, known as "browning", has received attention as a novel potential anti-obesity strategy. The expression of some characteristic genes including PR domain containing 16 is induced during the browning process. Although acetate has been reported to suppress weight gain in both rodents and humans, its potential effects on beige adipogenesis in white adipose tissue have not been fully characterized. We examined the effects of acetate treatment on 3T3-L1 cells and in obese diabetic KK-Ay mice...
November 2016: Journal of Clinical Biochemistry and Nutrition
https://www.readbyqxmd.com/read/27893612/the-influence-of-timing-and-frequency-of-adipose-derived-mesenchymal-stem-cell-therapy-on-immunomodulation-outcomes-after-vascularized-composite-allotransplantation
#10
Jan A Plock, Jonas T Schnider, Riccardo Schweizer, Wensheng Zhang, Wakako Tsuji, Matthias Waldner, Mario G Solari, Kacey G Marra, J Peter Rubin, Vijay S Gorantla
BACKGROUND: Cellular therapies for immunomodulation in vascularized composite allotransplantation (VCA) have gained importance due to their potential minimization of immunosuppression. Adipose-derived mesenchymal stem cells (AD-MSCs) especially have shown encouraging potential. We investigated the influence of timing and frequency of AD-MSC-treatment on immunologic and graft survival as well as graft vasculopathy (GV) outcomes after VCA. METHODS: Lewis (LEW) rats received full-mismatched Brown Norway (BN) rat hindlimb transplants...
November 23, 2016: Transplantation
https://www.readbyqxmd.com/read/27891610/resveratrol-supplementation-to-high-fat-diet-fed-pregnant-mice-promotes-brown-and-beige-adipocyte-development-and-prevents-obesity-in-male-offspring
#11
Tiande Zou, Daiwen Chen, Qiyuan Yang, Bo Wang, Mei-Jun Zhu, Peter W Nathanielsz, Min Du
Promoting beige/brite adipogenesis and thermogenic activity is considered as a promising therapeutic approach to reduce obesity and metabolic syndrome. Maternal obesity impairs offspring brown adipocyte function and correlates with obesity in offspring. We previously found that dietary resveratrol (RES) induces beige adipocyte formation in adult mice. Here we further evaluated the effect of resveratrol supplementation to pregnant mice on offspring thermogenesis and energy expenditure. Female C57BL/6 J mice were fed a control diet (CON) or a high fat diet (HFD) with/without 0...
November 28, 2016: Journal of Physiology
https://www.readbyqxmd.com/read/27887867/evaluation-of-function-and-recovery-of-adipose-derived-stem-cells-after-exposure-to-paclitaxel
#12
William M Harris, Ping Zhang, Michael Plastini, Telisha Ortiz, Nikolas Kappy, Jefferson Benites, Edward Alexeev, Shaohua Chang, Ross Brockunier, Jeffrey P Carpenter, Spencer A Brown
BACKGROUND AIMS: Adipose-derived stem cells (ASCs) are considered to play a positive role in wound healing as evidenced by their increasing use in breast reconstructive procedures. After chemotherapy for breast cancer, poor soft tissue wound healing is a major problem. In the present study, the functional capabilities and recovery of ASCs after exposure to chemotherapeutic agent paclitaxel (PTX) using in vitro and ex vivo models were demonstrated. METHODS: Human ASCs were isolated from periumbilical fat tissue and treated with PTX at various concentrations...
November 22, 2016: Cytotherapy
https://www.readbyqxmd.com/read/27886210/physical-activity-energy-expenditure-and-defense-of-body-weight-in-melanocortin-4-receptor-deficient-male-rats
#13
Tariq I Almundarij, Mark E Smyers, Addison Spriggs, Lydia A Heemstra, Lisa Beltz, Eric Dyne, Caitlyn Ridenour, Colleen M Novak
Melanocortin 4 receptor (MC4R) variants contribute to human obesity, and rats lacking functional MC4R (Mc4r(K314X/K314X)) are obese. We investigated the hypothesis that low energy expenditure (EE) and physical activity contribute to this obese phenotype in male rats, and determined whether lack of functional MC4R conferred protection from weight loss during 50% calorie restriction. Though Mc4r(K314X/K314X) rats showed low brown adipose Ucp1 expression and were less physically active than rats heterozygous for the mutation (Mc4r(+/K314X)) or wild-type (Mc4r(+/+)) rats, we found no evidence of lowered EE in Mc4r(K314X/K314X) rats once body weight was taken into account using covariance...
November 25, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27883936/relationship-between-fgf21-and-ucp1-levels-under-time-restricted-feeding-and-high-fat-diet
#14
Nava Chapnik, Yoni Genzer, Oren Froy
Fibroblast growth factor 21 (FGF21) exhibits a circadian oscillation, and its induction is critical during fasting. When secreted by liver and skeletal muscle, FGF21 enhances thermogenic activity in brown adipose tissue (BAT) by utilizing uncoupling protein 1 (UCP1) to dissipate energy as heat. Recently, it has been reported that UCP1 is not required for FGF21-mediated reduction in body weight or improvements in glucose homeostasis. As the relationship between FGF21 and UCP1 induction in tissues other than BAT is less clear, we tested the effect of restricted feeding (RF) and high dietary fat on FGF21 circadian expression and its correlation with UCP1 expression in liver and white adipose tissue (WAT)...
November 2, 2016: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/27882370/anti-obesity-effects-of-arctii-fructus-arctium-lappa-in-white-brown-adipocytes-and-high-fat-diet-induced-obese-mice
#15
Yo-Han Han, Ji-Ye Kee, Dae-Seung Kim, Jinbong Park, Mi-Young Jeong, Jung-Geon Mun, Sung-Joo Park, Jong-Hyun Lee, Jae-Young Um, Seung-Heon Hong
Arctii Fructus is traditionally used in oriental pharmacies as an anti-inflammatory medicine. Although several studies have shown its anti-inflammatory effects, there have been no reports on its use in obesity related studies. In this study, the anti-obesity effect of Arctii Fructus was investigated in high-fat diet (HFD)-induced obese mice, and the effect was confirmed in white and primary cultured brown adipocytes. Arctii Fructus inhibited weight gain and reduced the mass of white adipose tissue in HFD-induced obese mice...
November 24, 2016: Food & Function
https://www.readbyqxmd.com/read/27881400/loss-of-ucp1-exacerbates-western-diet-induced-glycemic-dysregulation-independent-of-changes-in-body-weight-in-female-mice
#16
Nathan C Winn, Victoria J Vieira-Potter, Michelle L Gastecki, Rebecca J Welly, Rebecca J Scroggins, Terese M Zidon, T'Keaya L Gaines, Makenzie L Woodford, Natalia G Karasseva, Jill A Kanaley, Harold S Sacks, Jaume Padilla
We tested the hypothesis that female mice null for UCP1 would have increased susceptibility to Western diet-induced "whitening" of brown adipose tissue (AT) and glucose intolerance. Six-week old C57BL/6J wild-type (WT) and UCP1 knockout (UCP1(-/-)) mice, housed at 25°C, were randomized to either a control diet (10% kcal from fat) or Western diet (45% kcal from fat and 1% cholesterol) for 28 weeks. Loss of UCP1 had no effect on energy intake, energy expenditure, spontaneous physical activity, weight gain, or visceral white AT mass...
November 23, 2016: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
https://www.readbyqxmd.com/read/27881398/separate-and-shared-sympathetic-outflow-to-white-and-brown-fat-coordinately-regulate-thermoregulation-and-beige-adipocyte-recruitment
#17
Ngoc Ly T Nguyen, Candace L Barr, Vitaly Ryu, Qiang Cao, Bingzhong Xue, Timothy J Bartness
White adipose tissue (WAT) and brown adipose tissue (BAT) are innervated and regulated by the sympathetic nervous system (SNS). It is not clear, however, whether there are shared or separate central SNS outflows to WAT and BAT that regulate their function. We injected two isogenic strains of pseudorabies virus, a retrograde transneuronal viral tract tracer, with unique fluorescent reporters into interscapular BAT (IBAT) and inguinal WAT (IWAT) of the same Siberian hamsters to define SNS pathways to both. To test the functional importance of SNS coordinated control of BAT and WAT, we exposed hamsters with denervated SNS nerves to IBAT to 4°C for 16-24 hours, and measured core and fat temperatures, and norepinephrine turnover (NETO) and uncoupling protein 1 (UCP1) expression in fat tissues...
November 23, 2016: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
https://www.readbyqxmd.com/read/27876809/cold-induced-thermogenesis-in-humans
#18
REVIEW
R J Brychta, K Y Chen
A basic property of endothermic thermoregulation is the ability to generate heat by increasing metabolism in response to cold ambient temperatures to maintain a stable core body temperature. This process, known as cold-induced thermogenesis (CIT), has been measured in humans as early as 1780 by Antoine Lavoisier, but has found renewed interest because of the recent 'rediscovery' of thermogenic, cold-activated brown adipose tissue (BAT) in adult humans. In this review, we summarize some of the key findings of the work involving CIT over the past two centuries and highlight some of the seminal studies focused on this topic...
November 23, 2016: European Journal of Clinical Nutrition
https://www.readbyqxmd.com/read/27876792/mtorc1-is-required-for-brown-adipose-tissue-recruitment-and-metabolic-adaptation-to-cold
#19
Sébastien M Labbé, Mathilde Mouchiroud, Alexandre Caron, Blandine Secco, Elizaveta Freinkman, Guillaume Lamoureux, Yves Gélinas, Roger Lecomte, Yohan Bossé, Patricia Chimin, William T Festuccia, Denis Richard, Mathieu Laplante
In response to cold, brown adipose tissue (BAT) increases its metabolic rate and expands its mass to produce heat required for survival, a process known as BAT recruitment. The mechanistic target of rapamycin complex 1 (mTORC1) controls metabolism, cell growth and proliferation, but its role in regulating BAT recruitment in response to chronic cold stimulation is unknown. Here, we show that cold activates mTORC1 in BAT, an effect that depends on the sympathetic nervous system. Adipocyte-specific mTORC1 loss in mice completely blocks cold-induced BAT expansion and severely impairs mitochondrial biogenesis...
November 23, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27875786/inflammation-dysregulated-metabolism-and-aromatase-in-obesity-and-breast-cancer
#20
REVIEW
Heba Zahid, Evan R Simpson, Kristy A Brown
Obesity is associated with an increased risk of estrogen-dependent breast cancer after menopause. Adipose tissue undergoes important changes in obesity due to excess storage of lipids, leading to adipocyte cell death and the recruitment of macrophages. The resultant state of chronic low-grade inflammation is associated with the activation of NFkB signaling and elevated levels of aromatase, the rate-limiting enzyme in estrogen biosynthesis. This occurs not only in the visceral and subcutaneous fat, but also in the breast fat...
November 19, 2016: Current Opinion in Pharmacology
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