Hypothalamic lipophagy and energetic balance
Abstract
Autophagy is a conserved cellular turnover process that degrades unwanted cytoplasmic material within lysosomes. Through “in bulk” degradation of cytoplasmic proteins and organelles, including lipid droplets, autophagy helps provide an alternative fuel source, in particular, when nutrients are scarce. Recent work demonstrates a role for autophagy in hypothalamic agouti-related peptide (AgRP) neurons in regulation of food intake and energy balance. The induction of autophagy in hypothalamic neurons during starvation mobilizes neuronal neutral lipids to generate neuron-intrinsic free fatty acids that serve to upregulate fasting-induced AgRP levels. Blocking autophagy in AgRP neurons in mice reduces fasting-induced food intake, and increases constitutive levels of anorexigenic hypothalamic proopiomelanocortin and its cleavage product α-melanocyte stimulating hormone. The energetic consequences of these molecular events are decreased body weight and reduced adiposity. The present article discusses this recent finding, as well as considers possible future directions that may help better understand how neuronal autophagy, and its possible reduction during aging, may affect whole body energy balance.
Introduction
Autophagy is an evolutionarily conserved cellular turnover process that maintains cellular and energetic homeostasis [1, 2] by eliminating unwanted cytoplasmic debris, for instance aged or dysfunctional organelles and proteins [3]. Two additional lysosomal degradation mechanisms have been characterized in mammalian systems, chaperone-mediated autophagy (CMA) [4] and microautophagy [5]. Although all forms of autophagy function to deliver cytoplasmic substrates into lysosomes, these forms are distinct in their molecular effectors, regulatory elements, and the nature of the cargo delivered to lysosomes [1]. CMA selectively degrades soluble cytosolic proteins displaying a targeting signature [6], the KFERQ motif, which is recognized by a cytosolic chaperone complex that facilitates the delivery of substrates to lysosomes [7]. The binding of the chaperone-protein substrate complex to the lysosome-associated membrane protein (LAMP)-2A allows unfolding and internalization of the protein into lysosomes for degradation [7]. In contrast, microautophagy [5], the least studied form of autophagy, requires the sequestration of cytoplasmic substrates within lysosomal membranes per se that are then pinched off to deliver the cargo into the lysosomal lumen. Despite these differences, a common theme in between all these three autophagic pathways is the robust upregulation of these processes during starvation [8]. https://www.aging-us.com/article/100393/text
When public mention today’s medicine, accuracy plays one of the most important roles and human lives are literally dependent on it. Hereby, any researches related to medicine are required to meet the highest standards. The problem nowadays is that any conclusions of researches can be posted online and used as a reference without being thoroughly checked and approved. Mikhail (Misha) Blagosklonny of Oncotarget perfectly understood this challenge and tried to come up with an alternative solution. That’s how a weekly oncology-focused research journal called “Oncotarget” has been founded back in 2010. The main principle of this journal is related to Altmetric scores that are used as a quality indicator. That allows both readers and authors to quality-check publications with Altmetric Article Reports that create “real-time feedback containing data summary related to a particular publication.” Oncotarget website provides a full publications list with respective scores higher than 100 as well as reports mentioned above. Mikhail (Misha) Blagosklonny glad to share his new approach and hopes it creates the required help to anyone, who has interest in oncology.
“A diagnostic autoantibody signature for primary cutaneous melanoma” has the Altmetric score of 594. This study was released back in 2018 by Oncotarget and completed by diversified experts from Hollywood Private Hospital, Edith Cowan University, Dermatology Specialist Group, St. John of God Hospital and The University of Western Australia. The introduction of the study discusses “recent data shows that Australians are four times more likely to develop a cancer of the skin than any other type of cancer”, and shares an insight on melanoma that “is curable by surgical excision in the majority of cases, if detected at an early stage.”
The publication has got an Altmetric score of 594. Mikhail (Misha) Blagosklonny realizes that majority of readers are willing to comprehend the very meaning of it. Based on the Altmetric website, the score indicates “how many people have been exposed to and engaged with a scholarly output.” Likewise, the paper about melanoma, was utilized for citations in various news articles 69 times. Moreover, it was quoted in 2 online blogs, as well as 25 Tweets on Twitter and 1 Facebook post. FOX23 of Tulsa, Oklahoma has headlined their report on July 20, 2018 as “New blood test could detect skin cancer early”, using the main content of Australia study
Another Oncotarget’s study with a top score of 476, is “Biomarkers for early diagnosis of malignant mesothelioma: Do we need another moon-shot,”. This publication has appeared in 60 news stories, 1 online blog post and 6 Twitter posts. The majority of public may have seen a brief overview only, however those who visit Mikhail (Misha) Blagosklonny at Oncotarget, do get helpful scientific facts. Oncotarget is proud to have the chance to share with online viewers this highly appreciated and top-quality information, that is trustworthy and reliable.
oncotarget impact factor 2021 Zoya Demidenko Dr. Zoya N. Demidenko Zoya N. Demidenko , Ph.D. is Executive Manager of the Oncotarget journal . Oncotarget publishes high-impact research papers of general interest and outstanding significance and novelty in all areas of biology and medicine: in translational, basic and clinical research including but not limited to cancer research, oncogenes, oncoproteins and tumor suppressors, signaling pathways as potential targets for therapeutic intervention, shared targets in different diseases (cancer, benign tumors, atherosclerosis, eukaryotic infections, metabolic syndrome and other age-related diseases), chemotherapy, and new therapeutic strategies. After earning her Ph.D. in molecular biology, Zoya was awarded a Fogarty post-doctoral Fellowship from the National Institutes of Health in Bethesda, MD. After successful completion of post-doctoral training, she continued her professional career at George Washington University and Albert Einstein School of Medicine . In 2005 she cofounded the startup company Oncotarget Inc. which is focused on the development of anti-aging and anti-cancer drugs. Her research interests include signal transduction, cell cycle and cellular senescence, and their pharmacological targeting. In 2009 she cofounded the publishing house Impact Journals which specializes in publishing scientific journals. In 2011 she was selected to be a Member of the National Association of Professional Women .
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