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Full-Text Articles in Life Sciences

Mtorc2/Akt Activation In Adipocytes Is Required For Adipose Tissue Inflammation In Tuberculosis, Nuria Martinez, Catherine Y. Cheng, Natkunam Ketheesan, Aidan Cullen, Yuefeng Tang, Josephine Lum, Kim West, Michael Poidinger, David A. Guertin, Amit Singhal, Hardy Kornfeld Jul 2019

Mtorc2/Akt Activation In Adipocytes Is Required For Adipose Tissue Inflammation In Tuberculosis, Nuria Martinez, Catherine Y. Cheng, Natkunam Ketheesan, Aidan Cullen, Yuefeng Tang, Josephine Lum, Kim West, Michael Poidinger, David A. Guertin, Amit Singhal, Hardy Kornfeld

Open Access Articles

BACKGROUND: Mycobacterium tuberculosis has co-evolved with the human host, adapting to exploit the immune system for persistence and transmission. While immunity to tuberculosis (TB) has been intensively studied in the lung and lymphoid system, little is known about the participation of adipose tissues and non-immune cells in the host-pathogen interaction during this systemic disease.

METHODS: C57BL/6J mice were aerosol infected with M. tuberculosis Erdman and presence of the bacteria and the fitness of the white and brown adipose tissues, liver and skeletal muscle were studied compared to uninfected mice.

FINDINGS: M. tuberculosis infection in mice stimulated immune cell infiltration ...


Hepatic Dysfunction Caused By Consumption Of A High-Fat Diet, Anthony R. Soltis, Norman J. Kennedy, Xiaofeng Xin, Feng Zhou, Scott B. Ficarro, Yoon Sing Yap, Bryan J. Matthews, Douglas A. Lauffenburger, Forest M. White, Jarrod A. Marto, Roger J. Davis, Ernest Fraenkel Dec 2017

Hepatic Dysfunction Caused By Consumption Of A High-Fat Diet, Anthony R. Soltis, Norman J. Kennedy, Xiaofeng Xin, Feng Zhou, Scott B. Ficarro, Yoon Sing Yap, Bryan J. Matthews, Douglas A. Lauffenburger, Forest M. White, Jarrod A. Marto, Roger J. Davis, Ernest Fraenkel

University of Massachusetts Medical School Faculty Publications

Obesity is a major human health crisis that promotes insulin resistance and, ultimately, type 2 diabetes. The molecular mechanisms that mediate this response occur across many highly complex biological regulatory levels that are incompletely understood. Here, we present a comprehensive molecular systems biology study of hepatic responses to high-fat feeding in mice. We interrogated diet-induced epigenomic, transcriptomic, proteomic, and metabolomic alterations using high-throughput omic methods and used a network modeling approach to integrate these diverse molecular signals. Our model indicated that disruption of hepatic architecture and enhanced hepatocyte apoptosis are among the numerous biological processes that contribute to early liver ...


Decreasing Cb1 Receptor Signaling In Kupffer Cells Improves Insulin Sensitivity In Obese Mice, Tony Jourdan, Sarah M. Nicoloro, Zhou Zhou, Yuefei Shen, Jie Liu, Nathan J. Coffey, Resat Cinar, Grzegorz Godlewski, Bin Gao, Myriam Aouadi, Michael P. Czech, George Kunos Nov 2017

Decreasing Cb1 Receptor Signaling In Kupffer Cells Improves Insulin Sensitivity In Obese Mice, Tony Jourdan, Sarah M. Nicoloro, Zhou Zhou, Yuefei Shen, Jie Liu, Nathan J. Coffey, Resat Cinar, Grzegorz Godlewski, Bin Gao, Myriam Aouadi, Michael P. Czech, George Kunos

UMass Metabolic Network Publications

OBJECTIVE: Obesity-induced accumulation of ectopic fat in the liver is thought to contribute to the development of insulin resistance, and increased activity of hepatic CB1R has been shown to promote both processes. However, lipid accumulation in liver can be experimentally dissociated from insulin resistance under certain conditions, suggesting the involvement of additional mechanisms. Obesity is also associated with pro-inflammatory changes which, in turn, can promote insulin resistance. Kupffer cells (KCs), the liver's resident macrophages, are the major source of pro-inflammatory cytokines in the liver, such as TNF-alpha, which has been shown to inhibit insulin signaling in multiple cell types ...


Emerging Evidence For Beneficial Macrophage Functions In Atherosclerosis And Obesity-Induced Insulin Resistance, Timothy P. Fitzgibbons, Michael P. Czech Mar 2016

Emerging Evidence For Beneficial Macrophage Functions In Atherosclerosis And Obesity-Induced Insulin Resistance, Timothy P. Fitzgibbons, Michael P. Czech

University of Massachusetts Medical School Faculty Publications

The discovery that obesity promotes macrophage accumulation in visceral fat led to the emergence of a new field of inquiry termed "immunometabolism". This broad field of study was founded on the premise that inflammation and the corresponding increase in macrophage number and activity was a pathologic feature of metabolic diseases. There is abundant data in both animal and human studies that supports this assertation. Established adverse effects of inflammation in visceral fat include decreased glucose and fatty acid uptake, inhibition of insulin signaling, and ectopic triglyceride accumulation. Likewise, in the atherosclerotic plaque, macrophage accumulation and activation results in plaque expansion ...


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 ...


Genetic Deficiency Of Cd40 In Mice Exacerbates Metabolic Manifestations Of Diet-Induced Obesity: A Dissertation, Chang-An Guo Apr 2013

Genetic Deficiency Of Cd40 In Mice Exacerbates Metabolic Manifestations Of Diet-Induced Obesity: A Dissertation, Chang-An Guo

GSBS Dissertations and Theses

The past two decades have seen an explosive increase of obesity rates worldwide, with more than one billion adults overweight and 300 million of them obese. Obesity and its associated complications have become leading causes of morbidity and mortality in the United States and major contributing factors to the rising costs of national health care.

The pathophysiology of obesity and type 2 diabetes in rodents and humans is characterized by low-grade inflammation and chronic activation of immune pathways in adipose tissue and liver. The CD40 receptor and its ligand, CD40L, initiate immune cell signaling promoting inflammation, but conflicting data on ...