Article
Cell Biology
John D. Griffin, Eloy Bejarano, Xiang-Dong Wang, Andrew S. Greenberg
Summary: The data suggest that protection against NAFLD in the absence of hepatic PLIN2 is driven by the integrated actions of both ATGL and lipophagy, with increased autophagy contributing to enhanced cellular fatty acid oxidation in PLIN2(LKO) hepatocytes. Inhibiting either ATGL or autophagy blunted the increased FA oxidation, while combined inhibition of both pathways reduced FA oxidation to the same extent as treatment with either inhibitor alone.
Article
Chemistry, Multidisciplinary
Gernot F. Grabner, Nikolaus Guttenberger, Nicole Mayer, Anna K. Migglautsch-Sulzer, Christian Lembacher-Fadum, Nermeen Fawzy, Dominik Bulfon, Peter Hofer, Thomas Zuellig, Lennart Hartig, Natalia Kulminskaya, Gabriel Chalhoub, Margarita Schratter, Franz P. W. Radner, Karina Preiss-Landl, Sarah Masser, Achim Lass, Rudolf Zechner, Karl Gruber, Monika Oberer, Rolf Breinbauer, Robert Zimmermann
Summary: This study reports the development and biological characterization of the first small-molecule inhibitor of human ATGL. This inhibitor selectively inactivates ATGL in humans and nonhuman primates, providing a potential therapeutic option for lipotoxicity-driven disorders.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Review
Biochemistry & Molecular Biology
Marek Wilhelm, Lenka Rossmeislova, Michaela Siklova
Summary: This article reviews the characteristics of lipogenic and lipolytic enzymes and the methods available for measuring their activity. It evaluates the applicability of these methods to different biological samples and discusses the advantages and disadvantages of these methods in vivo, ex vivo, and in vitro.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Medicine, Research & Experimental
Jennifer Guerrero-Santoro, Mayumi Morizane, Soo-Young Oh, Takuya Mishima, Julie P. Goff, Ibrahim Bildirici, Elena Sadovsky, Yingshi Ouyang, Vladimir A. Tyurin, Yulia Y. Tyurina, Valerian E. Kagan, Yoel Sadovsky
Summary: In eutherians, the placenta is crucial for the uptake, storage, and metabolism of lipids. However, the regulation of placental lipid droplet lipolysis remains unknown. This study found that the absence of CGI58, not PNPLA2, significantly increased placental lipid droplet accumulation. Additionally, PNPLA9 contributed to lipolysis in human placental trophoblasts.
Article
Biochemistry & Molecular Biology
Satoru Mukai, Akiko Mizokami, Takahito Otani, Tomomi Sano, Miho Matsuda, Sakura Chishaki, Jing Gao, Tomoyo Kawakubo-Yasukochi, Ronghao Tang, Takashi Kanematsu, Hiroshi Takeuchi, Eijiro Jimi, Masato Hirata
Summary: GPRC6A regulates various physiological processes in response to its interaction with multiple ligands and its constitutive activation in adipocytes plays a key role in adipose lipid handling and the prevention of obesity and related metabolic disorders.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Oncology
Supreet Kaur, Christopher Auger, Dalia Barayan, Priyal Shah, Anna Matveev, Carly M. Knuth, Thurl E. Harris, Marc G. Jeschke
Summary: Hypermetabolism following severe burn injuries can lead to adipocyte dysfunction and other adverse consequences, with adipose triglyceride lipase (ATGL) playing a crucial role in regulating these processes. Targeting ATGL may reduce adipose tissue changes and improve patient outcomes, as demonstrated by selective ATGL inhibitor studies.
CLINICAL AND TRANSLATIONAL MEDICINE
(2021)
Review
Endocrinology & Metabolism
Gernot F. Grabner, Hao Xie, Martina Schweiger, Rudolf Zechner
Summary: This review discusses the significant revisions in the understanding of intracellular lipolysis over the past two decades, focusing on how it affects lipid-mediated signaling, metabolic regulation, and energy homeostasis in multiple organs. The review also explores how these processes impact disease pathogenesis and how targeting lipolysis could potentially prevent or treat various diseases.
Review
Biochemistry & Molecular Biology
Sander Kersten
Summary: Fasting and starvation have been significant environmental factors that have shaped human energy metabolism. Humans adapt to fasting through time-dependent changes in energy metabolism, including the breakdown of liver glycogen, muscle protein, and fat stores. This paper provides an overview of the effects of fasting on adipose tissue metabolism, including the inhibition of lipoprotein lipase activity and activation of adipose triglyceride lipase.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS
(2023)
Article
Oncology
Julie Cremer, Laura Brohee, Laura Dupont, Camille Lefevre, Raphael Peiffer, Alicia M. Saarinen, Olivier Peulen, Laure Bindels, Jun Liu, Alain Colige, Christophe F. Deroanne
Summary: Bidirectional interactions between cancer cells and adipocytes in the microenvironment play a critical role in tumor progression. Acidification of the extracellular medium induced by cancer cells promotes preadipocyte lipolysis, which affects the phenotype of cancer cells and their response to chemotherapy. G0S2 is identified as the main regulator of cancer-induced lipolysis, and its adipocyte-specific overexpression inhibits mammary tumor growth and lung metastasis.
Article
Biochemistry & Molecular Biology
Tianjiao Li, Wei Guo, Zhanxiang Zhou
Summary: Understanding the regulation of ATGL in the liver is crucial for understanding lipid and glucose homeostasis and developing targeted therapies for hepatic metabolic disorders.
Article
Biochemistry & Molecular Biology
Rahim Zareie, Emad Yuzbashian, Hamed Rahimi, Golaleh Asghari, Maryam Zarkesh, Mehdi Hedayati, Abolghassem Djazayery, Ariyo Movahedi, Parvin Mirmiran, Alireza Khalaj
Summary: In non-obese adults, gene expressions of ATGL and HSL in SAT were associated with dietary fat quantity and composition, while no associations were observed in obese individuals and non-obese individuals' VAT.
PROSTAGLANDINS LEUKOTRIENES AND ESSENTIAL FATTY ACIDS
(2021)
Article
Nutrition & Dietetics
Zhizheng Fang, Lu Wei, Yanping Lv, Tongsheng Wang, Hamizah Shahirah Hamezah, Rongchun Han, Xiaohui Tong
Summary: This study investigates the impact of Phillyrin on obesity-related metabolic dysfunctions. It was found that Phillyrin reduces circulating level of glycerol, hepatic steatosis, and improves insulin sensitivity in obese mice. Phillyrin also attenuates obesity-related inflammation and IL-6 production in adipose tissue. Furthermore, Phillyrin inhibits IL-6-initiated basal lipolysis and expression of adipose triglyceride lipase (ATGL) in adipose tissue. These findings suggest that Phillyrin can be a potential candidate in the treatment of obesity-associated complications.
FRONTIERS IN NUTRITION
(2022)
Editorial Material
Endocrinology & Metabolism
Melissa A. Linden, Susan J. Burke, Humza A. Pirzadah, Tai-Yu Huang, Heidi M. Batdorf, Walid K. Mohammed, Katarina A. Jones, Sujoy Ghosh, Shawn R. Campagna, J. Jason Collier, Robert C. Noland
Summary: Glucocorticoid therapy can cause iatrogenic diabetes, and activating lipolysis plays a crucial role in its development. Inhibiting lipolysis can reduce glucocorticoid-induced obesity and hyperglycemia. The role of lipolysis differs between skeletal muscle and liver.
MOLECULAR METABOLISM
(2023)
Article
Biochemistry & Molecular Biology
Rajakumar Selvaraj, Sarah Zehnder, Russell Watts, Jihong Lian, Chinmayee Das, Randal Nelson, Richard Lehner
Summary: Two distinct diacylglycerol acyltransferases (DGAT1 and DGAT2) catalyze the final step of TG synthesis in hepatocytes. TG is either stored in cytosolic LDs or assembled into VLDLs in the ER. DGAT1-made TG is stored in smaller LDs while DGAT2-made TG is stored in larger LDs. ATGL targets DGAT1-generated LDs and the fatty acids released from these LDs are preferentially used for oxidation.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS
(2023)
Article
Endocrinology & Metabolism
Yusuke Nakatsu, Takeshi Yamamotoya, Mizuki Okumura, Tetsuhiro Ishii, Mayu Kanamoto, Miki Naito, Mikako Nakanishi, Shunya Aoyama, Yasuka Matsunaga, Akifumi Kushiyama, Hideyuki Sakoda, Midori Fujishiro, Hiraku Ono, Tomoichiro Asano
Summary: Deleting the Pin1 gene in epiWAT promotes lipolysis and increases ATGL protein expression. Pin1 directly associates with ATGL, enhancing its degradation through the ubiquitin proteasome system. AdipoPin1 KO mice under a high fat diet exhibit higher lipolytic activity and improved glucose metabolism.
METABOLISM-CLINICAL AND EXPERIMENTAL
(2021)