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University of Massachusetts Medical School

Cellular and Molecular Physiology

Liver

Articles 1 - 4 of 4

Full-Text Articles in Life Sciences

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 ...


Multi-Dimensional Transcriptional Remodeling By Physiological Insulin In Vivo, Thiago M. Batista, Ruben Garcia-Martin, Weikang Cai, Masahiro Konishi, Brian T. O'Neill, Masaji Sakaguchi, Jong Hun Kim, Dae Young Jung, Jason K. Kim, C. Ronald Kahn Mar 2019

Multi-Dimensional Transcriptional Remodeling By Physiological Insulin In Vivo, Thiago M. Batista, Ruben Garcia-Martin, Weikang Cai, Masahiro Konishi, Brian T. O'Neill, Masaji Sakaguchi, Jong Hun Kim, Dae Young Jung, Jason K. Kim, C. Ronald Kahn

Open Access Articles

Regulation of gene expression is an important aspect of insulin action but in vivo is intertwined with changing levels of glucose and counter-regulatory hormones. Here we demonstrate that under euglycemic clamp conditions, physiological levels of insulin regulate interrelated networks of more than 1,000 transcripts in muscle and liver. These include expected pathways related to glucose and lipid utilization, mitochondrial function, and autophagy, as well as unexpected pathways, such as chromatin remodeling, mRNA splicing, and Notch signaling. These acutely regulated pathways extend beyond those dysregulated in mice with chronic insulin deficiency or insulin resistance and involve a broad network of ...


Hypothalamic Ampk-Er Stress-Jnk1 Axis Mediates The Central Actions Of Thyroid Hormones On Energy Balance, Noelia Martinez-Sanchez, Roger J. Davis, Miguel Lopez Jul 2017

Hypothalamic Ampk-Er Stress-Jnk1 Axis Mediates The Central Actions Of Thyroid Hormones On Energy Balance, Noelia Martinez-Sanchez, Roger J. Davis, Miguel Lopez

UMass Metabolic Network Publications

Thyroid hormones (THs) act in the brain to modulate energy balance. We show that central triiodothyronine (T3) regulates de novo lipogenesis in liver and lipid oxidation in brown adipose tissue (BAT) through the parasympathetic (PSNS) and sympathetic nervous system (SNS), respectively. Central T3 promotes hepatic lipogenesis with parallel stimulation of the thermogenic program in BAT. The action of T3 depends on AMP-activated protein kinase (AMPK)-induced regulation of two signaling pathways in the ventromedial nucleus of the hypothalamus (VMH): decreased ceramide-induced endoplasmic reticulum (ER) stress, which promotes BAT thermogenesis, and increased c-Jun N-terminal kinase (JNK) activation, which controls hepatic lipid ...


Determination Of Fatty Acid Oxidation And Lipogenesis In Mouse Primary Hepatocytes, Thomas E. Akie, Marcus P. Cooper Aug 2015

Determination Of Fatty Acid Oxidation And Lipogenesis In Mouse Primary Hepatocytes, Thomas E. Akie, Marcus P. Cooper

GSBS Student Publications

Lipid metabolism in liver is complex. In addition to importing and exporting lipid via lipoproteins, hepatocytes can oxidize lipid via fatty acid oxidation, or alternatively, synthesize new lipid via de novo lipogenesis. The net sum of these pathways is dictated by a number of factors, which in certain disease states leads to fatty liver disease. Excess hepatic lipid accumulation is associated with whole body insulin resistance and coronary heart disease. Tools to study lipid metabolism in hepatocytes are useful to understand the role of hepatic lipid metabolism in certain metabolic disorders. In the liver, hepatocytes regulate the breakdown and synthesis ...