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Articles 1 - 7 of 7

Full-Text Articles in Biochemistry, Biophysics, and Structural Biology

Adipocyte Acly Facilitates Dietary Carbohydrate Handling To Maintain Metabolic Homeostasis In Females, Sully Fernandez, John M. Viola, Annmarie Torres, Martina Wallace, Sophie Trefely, Steven Zhao, Hayley C. Affronti, Jivani M. Gengatharan, David A. Guertin, Nathaniel W. Snyder, Christian M. Metallo, Kathryn E. Wellen May 2019

Adipocyte Acly Facilitates Dietary Carbohydrate Handling To Maintain Metabolic Homeostasis In Females, Sully Fernandez, John M. Viola, Annmarie Torres, Martina Wallace, Sophie Trefely, Steven Zhao, Hayley C. Affronti, Jivani M. Gengatharan, David A. Guertin, Nathaniel W. Snyder, Christian M. Metallo, Kathryn E. Wellen

Open Access Articles

Sugars and refined carbohydrates are major components of the modern diet. ATP-citrate lyase (ACLY) is upregulated in adipocytes in response to carbohydrate consumption and generates acetyl-coenzyme A (CoA) for both lipid synthesis and acetylation reactions. Here, we investigate the role of ACLY in the metabolic and transcriptional responses to carbohydrates in adipocytes and unexpectedly uncover a sexually dimorphic function in maintaining systemic metabolic homeostasis. When fed a high-sucrose diet, Acly(FAT-/-) females exhibit a lipodystrophy-like phenotype, with minimal fat accumulation, insulin resistance, and hepatic lipid accumulation, whereas Acly(FAT-/-) males have only mild metabolic phenotypes. We find that ACLY is ...


Exercise Rescues Gene Pathways Involved In Vascular Expansion And Promotes Functional Angiogenesis In Subcutaneous White Adipose Tissue, So Yun Min, Heather Learnard, Shashi Kant, Olga Gaelikman, Raziel Rojas-Rodriguez, Tiffany Desouza, Anand Desai, John F. Keaney Jr., Silvia Corvera, Siobhan M. Craige Apr 2019

Exercise Rescues Gene Pathways Involved In Vascular Expansion And Promotes Functional Angiogenesis In Subcutaneous White Adipose Tissue, So Yun Min, Heather Learnard, Shashi Kant, Olga Gaelikman, Raziel Rojas-Rodriguez, Tiffany Desouza, Anand Desai, John F. Keaney Jr., Silvia Corvera, Siobhan M. Craige

Open Access Articles

Exercise mitigates chronic diseases such as diabetes, cardiovascular diseases, and obesity; however, the molecular mechanisms governing protection from these diseases are not completely understood. Here we demonstrate that exercise rescues metabolically compromised high fat diet (HFD) fed mice, and reprograms subcutaneous white adipose tissue (scWAT). Using transcriptomic profiling, scWAT was analyzed for HFD gene expression changes that were rescued by exercise. Gene networks involved in vascularization were identified as prominent targets of exercise, which led us to investigate the vasculature architecture and endothelial phenotype. Vascular density in scWAT was found to be compromised in HFD, and exercise rescued this defect ...


Investigating The Interplay Of Physiological And Molecular Mechanisms Underpinning Programmable Aspects Of Heat Stress In Pigs, Jacob Seibert Jan 2018

Investigating The Interplay Of Physiological And Molecular Mechanisms Underpinning Programmable Aspects Of Heat Stress In Pigs, Jacob Seibert

Graduate Theses and Dissertations

Heat stress (HS) undermines production efficiency in all animal agriculture, culminating in major economic losses annually. The effects of HS in pigs is realized through depressed growth, altered body composition, and impaired reproductive performance. Pigs, unlike other mammals, do not possess functional sweat glands, making them rely on other mechanisms to thermoregulate during a heat challenge. Continual investigation of hyperthermia in pigs is crucial for developing new strategies and/or technologies that mitigate the effects of HS imposed on the pork industry. The studies conducted in this dissertation investigate the complex interplay of whole-animal physiology as well as cellular and ...


Nrg4 Promotes Fuel Oxidation And A Healthy Adipokine Profile To Ameliorate Diet-Induced Metabolic Disorders, Zhimin Chen, Guo-Xiao Wang, Sara L. Ma, Dae Young Jung, Hyekyung Ha, Tariq Altamimi, Xu-Yun Zhao, Liang Guo, Peng Zhang, Chun-Rui Hu, Ji-Xin Cheng, Gary D. Lopaschuk, Jason K. Kim, Jiandie D. Lin Aug 2017

Nrg4 Promotes Fuel Oxidation And A Healthy Adipokine Profile To Ameliorate Diet-Induced Metabolic Disorders, Zhimin Chen, Guo-Xiao Wang, Sara L. Ma, Dae Young Jung, Hyekyung Ha, Tariq Altamimi, Xu-Yun Zhao, Liang Guo, Peng Zhang, Chun-Rui Hu, Ji-Xin Cheng, Gary D. Lopaschuk, Jason K. Kim, Jiandie D. Lin

UMass Metabolic Network Publications

OBJECTIVE: Brown and white adipose tissue exerts pleiotropic effects on systemic energy metabolism in part by releasing endocrine factors. Neuregulin 4 (Nrg4) was recently identified as a brown fat-enriched secreted factor that ameliorates diet-induced metabolic disorders, including insulin resistance and hepatic steatosis. However, the physiological mechanisms through which Nrg4 regulates energy balance and glucose and lipid metabolism remain incompletely understood. The aims of the current study were: i) to investigate the regulation of adipose Nrg4 expression during obesity and the physiological signals involved, ii) to elucidate the mechanisms underlying Nrg4 regulation of energy balance and glucose and lipid metabolism, and ...


Amplification Of Adipogenic Commitment By Vstm2a, Blandine Secco, Peter L. Lee, David A. Guertin, Mathieu Laplante Jan 2017

Amplification Of Adipogenic Commitment By Vstm2a, Blandine Secco, Peter L. Lee, David A. Guertin, Mathieu Laplante

UMass Metabolic Network Publications

Despite progress in our comprehension of the mechanisms regulating adipose tissue development, the nature of the factors that functionally characterize adipose precursors is still elusive. Defining the early steps regulating adipocyte development is needed for the generation of tools to control adipose tissue size and function. Here, we report the discovery of V-set and transmembrane domain containing 2A (VSTM2A) as a protein expressed and secreted by committed preadipocytes. VSTM2A expression is elevated in the early phases of adipogenesis in vitro and adipose tissue development in vivo. We show that VSTM2A-producing cells associate with the vasculature and express the common surface ...


Systemic Insulin Sensitivity Is Regulated By Gps2 Inhibition Of Akt Ubiquitination And Activation In Adipose Tissue, Carly T. Cederquist, Claudia Lentucci, Camila Martinez Calejman, Vanessa Hayashi, Joseph Orofino, David A. Guertin, Susan K. Fried, Mi-Jeong Lee, M. Dafne Cardamone, Valentina Perissi Jan 2017

Systemic Insulin Sensitivity Is Regulated By Gps2 Inhibition Of Akt Ubiquitination And Activation In Adipose Tissue, Carly T. Cederquist, Claudia Lentucci, Camila Martinez Calejman, Vanessa Hayashi, Joseph Orofino, David A. Guertin, Susan K. Fried, Mi-Jeong Lee, M. Dafne Cardamone, Valentina Perissi

Open Access Articles

OBJECTIVE: Insulin signaling plays a unique role in the regulation of energy homeostasis and the impairment of insulin action is associated with altered lipid metabolism, obesity, and Type 2 Diabetes. The main aim of this study was to provide further insight into the regulatory mechanisms governing the insulin signaling pathway by investigating the role of non-proteolytic ubiquitination in insulin-mediated activation of AKT.

METHODS: The molecular mechanism of AKT regulation through ubiquitination is first dissected in vitro in 3T3-L1 preadipocytes and then validated in vivo using mice with adipo-specific deletion of GPS2, an endogenous inhibitor of Ubc13 activity (GPS2-AKO mice).

RESULTS ...


A Major Role Of Insulin In Promoting Obesity-Associated Adipose Tissue Inflammation, David J. Pedersen, Adilson L Guilherme, Laura V. Danai, Lauren Heyda, Anouch Matevossian, Jessica L. Cohen, Sarah M. Nicoloro, Juerg R. Straubhaar, Hye Lim Noh, Dae Young Jung, Jason K. Kim, Michael P. Czech May 2015

A Major Role Of Insulin In Promoting Obesity-Associated Adipose Tissue Inflammation, David J. Pedersen, Adilson L Guilherme, Laura V. Danai, Lauren Heyda, Anouch Matevossian, Jessica L. Cohen, Sarah M. Nicoloro, Juerg R. Straubhaar, Hye Lim Noh, Dae Young Jung, Jason K. Kim, Michael P. Czech

Open Access Articles

OBJECTIVE: Adipose tissue (AT) inflammation is associated with systemic insulin resistance and hyperinsulinemia in obese rodents and humans. A longstanding concept is that hyperinsulinemia may promote systemic insulin resistance through downregulation of its receptor on target tissues. Here we tested the novel hypothesis that insulin also impairs systemic insulin sensitivity by specifically enhancing adipose inflammation.

METHODS: Circulating insulin levels were reduced by about 50% in diet-induced and genetically obese mice by treatments with diazoxide or streptozotocin, respectively. We then examined AT crown-like structures, macrophage markers and pro-inflammatory cytokine expression in AT. AT lipogenesis and systemic insulin sensitivity was also monitored ...