Mitochondria, obesity and aging

Vernochet, Cecile; Kahn, C. Ronald

doi:10.18632/aging.100518

Cited by 21 publications

(15 citation statements)

References 5 publications

(7 reference statements)

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“…Defective mitochondrial functionality and visceral adipose tissue expansion are crucial footprints of age-related metabolic disorders [ 26 - 27 ]. Dietary or nutrient restriction such as fasting represents a strong physiological stimulus that links geroprotection to improved mitochondrial metabolism and fat mass remodeling [ 6 - 7 ].…”

Section: Discussionmentioning

confidence: 99%

Mitochondrial Hormesis links nutrient restriction to improved metabolism in fat cell

Lettieri-Barbato

Tatulli

Aquilano

et al. 2015

AgingHas erratum 2016-7-19

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Fasting promotes longevity by reprogramming metabolic and stress resistance pathways. However, although the impact on adipose tissue physiology through hormonal inputs is well established, the direct role of fasting on adipose cells is poorly understood. Herein we show that white and beige adipocytes, as well as mouse epididymal and subcutaneous adipose depots, respond to nutrient scarcity by acquiring a brown-like phenotype. Indeed, they improve oxidative metabolism through modulating the expression of mitochondrial-and nuclear-encoded oxidative phosphorylation genes as well as mitochondrial stress defensive proteins (UCP1, SOD2). Such adaptation is placed in a canonical mitohormetic response that proceeds via mitochondrial reactive oxygen species (mtROS) production and redistribution of FoxO1 transcription factor into nucleus. Nuclear FoxO1 (nFoxO1) mediates retrograde communication by inducing the expression of mitochondrial oxidative and stress defensive genes. Collectively, our findings describe an unusual white/beige fat cell response to nutrient availability highlighting another health-promoting mechanism of fasting.

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“…Mitochondrial DNA encodes 37 genes that are all essential for oxidative phosphorylation to generate ATP. This study indicates that the incidence of mitochondrial dysfunction increases after TRI; however, the exact mechanisms that associate mitochondrial dysfunction, obesity, and aging with metabolic syndrome remain a topic of debate (Pintus et al 2012;Vernochet and Kahn 2012). The mechanism of TRI-induced weight gain is unclear and is likely due to multiple factors.…”

Section: Discussionmentioning

confidence: 84%

Thoracic gamma irradiation-induced obesity in C57BL/6 female mice

Zhang

Yang

Zhang

et al. 2017

International Journal of Radiation Biology

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Purpose: To investigate the late effects of thoracic region irradiation (TRI) on mouse body weight. Materials and methods: Female C57BL/6 mice were divided into nonirradiated, 5 Gy total body irradiation, 9 Gy sub-total body irradiation, and 12.5 Gy thoracic region irradiation (TRI) groups. Changes in mouse weight were monitored every other week at similar time points for 12 months. The anatomical characteristics of abdominal visceral fat distribution were recorded, and mitochondrial DNA copy number in the hearts and livers and lipid metabolic signaling in the liver were analyzed. Data were analyzed by one-way analysis of variance and a student's t-test. Results: TRI led to a significant increase (p < .001) in body weight that was dependent on time and individuals [42.1% of mice were overweight (50% increase in body weight) 4 months post-TRI and 100% of mice were overweight at 10 months post-TRI]. Gross anatomical features of abdominal visceral fat distribution and storage in radiation-induced overweight/severely overweight mice were similar to those of high fat diet-induced overweight/severely overweight mice. The mitochondrial genome of heart and liver tissues from overweight/severely overweight mice had significantly (p < .05) decreased functional mitochondrial DNA copy number (ratios decreased from 1 to 0.71 or 0.49, respectively) and significantly (p < .05) increased mitochondrial DNA mutations (ratios increased from 1 to 3.21 or 1.83, respectively). CPT1 and IRS2 lipid metabolic signaling was significantly (p < .05-.01) decreased for both mRNA (fold decrease from 1 to 0.60 or 0.55, respectively) and protein (fold decrease from 1 to 0.62 or 0.19, respectively). Conclusions: TRI can cause mice to gain weight. These findings indicate that TRI can result in lipid metabolic abnormalities and provide a model to study the factors that result in these abnormalities. ARTICLE HISTORY

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“…Remarkably, mitochondrial dysfunction due to conditional knockout of mitochondrial transcription factor TFAM in adipose tissues was found to protect individuals against obesity [36]. Evidence from several studies in mice as well as humans supports the potential link between obesity and the levels of mitochondrial DNA in white adipose tissue.…”

Section: Mitochondrial Alterations In Obesitymentioning

confidence: 94%

Antibiotics-Induced Obesity: A Mitochondrial Perspective

Andrade

Jayaprakash²,

Bhat³

et al. 2017

Public Health Genomics

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Antibiotics are the first line of treatment against infections and have contributed immensely to reduce the morbidity and mortality rates. Recently, extensive use of antibiotics has led to alterations of the gut microbiome, predisposition to various diseases and most importantly, increase in the emergence of antibiotic-resistant bacteria, which poses a major threat to global public health. Another major issue faced worldwide due to unregulated use of antibiotics in children as well as in adults is the influence of metabolism and body weight homeostasis, leading to obesity. Apart from the involvement of biosocial causes influencing diet, physical activity, and antibiotic use, pathogenesis of obesity is linked to interconnected functional alterations in cells, tissues and organs due to biochemical, epigenetic and genetic factors. Mitochondrial dysfunction is one such factor, which is becoming the primary focus of various aspects of research on multifactorial complex diseases and is providing new perspectives on etiology, biomarker-based diagnosis, and drug sensitivity. Through this review, we have made an attempt to present the interplay between use of antibiotics, obesity, and associated mitochondrial dysfunction. This may provide insights into the molecular basis, genetic predisposition and environmental triggers, which in turn may have potential clinical applications in the management of antibiotic use.

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“…The underlying mechanism for how the obese state is causative to metabolic diseases is multifaceted and has been reviewed extensively [1-4]. Significant effort has focused on the pathological effect of obesity-induced ectopic fat deposition, or lipotoxicity, characterized by accumulation of lipid intermediates in non-adipose tissue [3, 4].…”

Section: Metabolic Flexibility In Energy Metabolismmentioning

confidence: 99%

Lipid metabolites as metabolic messengers in inter-organ communication

Liu

Alexander

Lee

2014

Trends in Endocrinology & Metabolism

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Metabolic homeostasis is achieved through coordinated regulation across several tissues. Studies using mouse genetic models have shown that perturbation of specific pathways of lipid metabolism in metabolically active tissues impacts systemic metabolic homeostasis. The use of metabolomic technologies combined with genetic models has helped identify several potential lipid mediators that serve as metabolic messengers to communicate energy status and modulate substrate utilization among tissues. When provided exogenously, these lipid metabolites exhibit biological effects on glucose and lipid metabolism, implicating a therapeutic potential for treating metabolic diseases. In this review, we will summarize recent advances in inter-organ communication through novel mechanisms with a focus on lipid mediators synthesized de novo or derived from dietary sources and discuss challenges and future directions.

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“…[1][2][3] For this reason, great effort has been dedicated to improve targeting ability and therapeutic efficacy of drug delivery systems. It is increasingly conspicuous that mitochondrial dysfunction is closely related to cancer progression, 4,5 as well as obesity, 6,7 diabetes, 8,9 and Alzheimer disease. 10,11 Known as powerhouse of cells, as well as the center of the cell programmed death pathway, mitochondria possess many proapoptotic and antiapoptotic proteins such as Bax, Bak, Noxa, Bcl-XL, and Bcl-2.…”

Section: Introductionmentioning

confidence: 99%

Improved mitochondrial targeting effect of HPMA copolymer by SS20 peptide mediation and nonendocytosis pathway

Liu

Xiong

et al. 2018

J Pep Sci

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Mitochondrion plays an important role in executing cell programmed death pathway.Therefore, drugs designed to target mitochondria are supposed to make superior contributions to cancer therapy. However, the problem that drugs or drug delivery systems being sequestrated in endosomes/lysosomes needs to be solved for effective drug delivery. Here, mitochondrial targeting and nonendocytic cell entry peptide SS20 modified HPMA copolymer (P-FITC-SS20) was synthesized. With SS20 peptide modification, the uptake behavior of HPMA copolymers changed remarkably compared with unmodified ones. The internalization of P-FITC-SS20 was not influenced by endocytic inhibitors and temperature. Further, the internalized copolymers were not trapped in endosomes/lysosomes. Although cellular uptake of HPMA copolymer was decreased after SS20 peptide modification, SS20 peptide significantly improved mitochondrial accumulation of HPMA copolymers due to its outstanding mitochondrial targeting ability. Moreover, owing to lower susceptibility to macrophagocyte in blood, P-SS20-Cy5 showed longer blood circulation time and enhanced tumor accumulation. The current study validated that SS20 peptide modification is a promising strategy for mitochondrial targeting drug delivery systems and can be further applied to mitochondria associated diseases to improve therapeutic efficacy.

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Mitochondria, obesity and aging

Cited by 21 publications

References 5 publications

Mitochondrial Hormesis links nutrient restriction to improved metabolism in fat cell

Thoracic gamma irradiation-induced obesity in C57BL/6 female mice

Antibiotics-Induced Obesity: A Mitochondrial Perspective

Lipid metabolites as metabolic messengers in inter-organ communication

Improved mitochondrial targeting effect of HPMA copolymer by SS20 peptide mediation and nonendocytosis pathway

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