Journal article
Lysosomes Mediate Benefits of Intermittent Fasting in Cardiometabolic Disease: The Janitor Is the Undercover Boss
COMPREHENSIVE PHYSIOLOGY, Vol.8(4), pp.1639-1667
09/14/2018
DOI: 10.1002/cphy.c180005
PMCID: PMC6423516
PMID: 30215867
Abstract
Adaptive responses that counter starvation have evolved over millennia to permit organismal survival, including changes at the level of individual organelles, cells, tissues, and organ systems. In the past century, a shift has occurred away from disease caused by insufficient nutrient supply toward overnutrition, leading to obesity and diabetes, atherosclerosis, and cardiometabolic disease. The burden of these diseases has spurred interest in fasting strategies that harness physiological responses to starvation, thus limiting tissue injury during metabolic stress. Insights gained from animal and human studies suggest that intermittent fasting and chronic caloric restriction extend lifespan, decrease risk factors for cardiometabolic and inflammatory disease, limit tissue injury during myocardial stress, and activate a cardioprotective metabolic program. Acute fasting activates autophagy, an intricately orchestrated lysosomal degradative process that sequesters cellular constituents for degradation, and is critical for cardiac homeostasis during fasting. Lysosomes are dynamic cellular organelles that function as incinerators to permit autophagy, as well as degradation of extracellular material internalized by endocytosis, macropinocytosis, and phagocytosis. The last decade has witnessed an explosion of knowledge that has shaped our understanding of lysosomes as central regulators of cellular metabolism and the fasting response. Intriguingly, lysosomes also store nutrients for release during starvation; and function as a nutrient sensing organelle to couple activation of mammalian target of rapamycin to nutrient availability. This article reviews the evidence for how the lysosome, in the guise of a janitor, may be the "undercover boss" directing cellular processes for beneficial effects of intermittent fasting and restoring homeostasis during feast and famine. (C) 2018 American Physiological Society.
Details
- Title: Subtitle
- Lysosomes Mediate Benefits of Intermittent Fasting in Cardiometabolic Disease: The Janitor Is the Undercover Boss
- Creators
- Kartik Mani - Washington University in St. LouisAli Javaheri - Washington University in St. LouisAbhinav Diwan - Washington University in St. Louis
- Resource Type
- Journal article
- Publication Details
- COMPREHENSIVE PHYSIOLOGY, Vol.8(4), pp.1639-1667
- DOI
- 10.1002/cphy.c180005
- PMID
- 30215867
- PMCID
- PMC6423516
- NLM abbreviation
- Compr Physiol
- eISBN
- 9780470650714; 0470650710
- ISSN
- 2040-4603
- eISSN
- 2040-4603
- Publisher
- Wiley
- Number of pages
- 29
- Grant note
- Children's Discovery Institute of Washington University School of Medicine K08HL138262-01 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA HL107594 / National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA John Cochran VA Medical Center I01BX000448; 1I01BX001969; I01BX004235 / Department of Veterans Affairs; US Department of Veterans Affairs St. Louis Children's Hospital
- Language
- English
- Date published
- 09/14/2018
- Academic Unit
- Internal Medicine
- Record Identifier
- 9984695828802771
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