Transcriptional profiling identifies strain-specific effects of caloric restriction and opposite responses in human and mouse white adipose tissue

Swindell, William R.; List, Edward O.; Berryman, Darlene E.; Kopchick, John J.

doi:10.18632/aging.101424

Cited by 9 publications

(6 citation statements)

References 84 publications

(122 reference statements)

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“…In humans, analyses from multiple studies indicates that both short-term (e.g., 4 weeks) and long-term (e.g., 1 year) CR upregulates transcriptome modules associated with stem cell maintenance, blood vessel remodeling, and lipid metabolism in subcutaneous fat tissue ( 31 ). Other studies indicate that very long-term (10 years) voluntary CR causes gene expression patterns related to enhanced lipid and glucose metabolism, and downregulation of the insulin/IGF-1 growth pathway (resulting in a younger transcriptional profile) in muscle (a main metabolic tissue), consistent with the pre-clinical mouse and non-human primate data ( 8 ).…”

Section: Calorie Restrictionmentioning

confidence: 99%

“…With CR (perhaps the most studied and robust nutritional intervention) for example, global plasma biomarker changes with CR in mice mimic those seen with fasting in humans ( 69 ), but recent research shows more divergent transcriptome effects of certain healthy nutritional interventions in mice and humans. For instance, an increase in stem cell maintenance and vascularization pathway activation is associated with CR in human subcutaneous white adipose tissue (WAT), but in mouse epididymal WAT these processes are downregulated with CR ( 31 ).…”

Section: Research Gaps and Future Directionsmentioning

confidence: 99%

“…However, It appears that CR results in greater lifespan extension in non-inbred mice when compared to inbred mice and may not be as effective in certain genetic backgrounds/strains ( 70 ). The underlying mechanisms are still under investigation, but some evidence shows that certain mouse strains exhibit completely opposite transcriptional responses to CR compared with other strains (e.g., BALBC, DBA), and these effects are tissue-specific ( 31 ). As such, when examining the influence of healthy nutritional interventions on the rodent transcriptome, it is important to consider the genetic strain/background and tissue(s) before drawing conclusions.…”

Section: Research Gaps and Future Directionsmentioning

confidence: 99%

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Transcriptomic Effects of Healthspan-Promoting Dietary Interventions: Current Evidence and Future Directions

Wahl

LaRocca

2021

Front. Nutr.

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Aging is the greatest risk factor most diseases, including cardiovascular disorders, cancers, diabetes, and neurodegeneration, but select nutritional interventions may profoundly reduce the risk for these conditions. These interventions include calorie restriction, intermittent fasting, protein restriction, and reducing intake of certain amino acids. Certain ad libitum diets, including the Mediterranean, Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability, and Okinawan diets also promote healthy aging. Evidence indicates that these dietary strategies influence aging and healthspan by acting on the biological “hallmarks of aging” and especially upstream nutrient sensing pathways. Recent advances in “omics” technologies, including RNA-sequencing (transcriptomics), have increased our understanding of how such nutritional interventions may influence gene expression related to these biological mediators of aging, primarily in pre-clinical studies. However, whether these effects are also reflected in the human transcriptome, which may provide insight on other downstream/related cellular processes with aging, is an emerging topic. Broadly, the investigation of how these nutritional interventions influence the transcriptome may provide novel insight into pathways associated with aging, and potential targets to treat age-associated disease and increase healthspan. Therefore, the purpose of this mini review is to summarize what is known about the transcriptomic effects of key dietary/nutritional interventions in both pre-clinical models and humans, address gaps in the literature, and provide insight into future research directions.

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Section: Calorie Restrictionmentioning

confidence: 99%

Section: Research Gaps and Future Directionsmentioning

confidence: 99%

Section: Research Gaps and Future Directionsmentioning

confidence: 99%

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Transcriptomic Effects of Healthspan-Promoting Dietary Interventions: Current Evidence and Future Directions

Wahl

LaRocca

2021

Front. Nutr.

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“…Accordingly, KO mice generated using 129 derived ES cells are routinely backcrossed onto a B6 background. Importantly, the 129 and B6 strains vary widely in their biology and in the pathology of multiple systems and organs, including aging, 2,3 behavior, 4–6 bone, 7 brain, 8–10 cancer, 11 cardiovascular biology, 12–14 cellular death, 15 coagulation, 16 immunology, 17–19 infection, 20–22 inflammation, 23,24 kidney, 25–27 liver, 28,29 metabolism, 30,31 neurology, 32,33 nutrition, 2 placenta, 34 reproductive biology, 35 skin, 36,37 transfusion, 30 and vascular biology 38 . Thus, if residual 129 genetic elements remain after backcrossing onto a B6 background, and one compares a KO strain to WT B6, then one risks mistaking a phenotypic difference between 129 and B6 mice for a result caused by the KO.…”

Section: Introductionmentioning

confidence: 99%

Mouse background genetics in biomedical research: The devil's in the details

et al. 2021

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Background: Genetically modified mice are used widely to explore mechanisms in most biomedical fields-including transfusion. Concluding that a gene modification is responsible for a phenotypic change assumes no other differences between the gene-modified and wild-type mice besides the targetted gene. Study Design and Methods:To test the hypothesis that the N-terminus of Band3, which regulates metabolism, affects RBC storage biology, RBCs from mice with a modified N-terminus of Band3 were stored under simulated blood bank conditions. All strains of mice were generated with the same initial embryonic stem cells from 129 mice and each strain was backcrossed with C57BL/6 (B6) mice. Both 24-h recoveries post-transfusion and metabolomics were determined for stored RBCs. Genetic profiles of mice were assessed by a high-resolution SNP array.Results: RBCs from mice with a mutated Band3 N-terminus had increased lipid oxidation and worse 24-h recoveries, "demonstrating" that Band3 regu-

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“…However, interspecies discrepancies impede possible translations of research findings. Amongst numerous obstacles, the significant negative correlations in gene regulation between mice and humans in caloric restriction make direct comparison prone to errors [46]. Further differences occur between sex and life stages.…”

Section: Introductionmentioning

confidence: 99%

Examination of ex-vivo viability of human adipose tissue slice culture

Schopow¹,

Kallendrusch²,

Gong³

et al. 2020

PLoS ONE

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Obesity is associated with significantly higher mortality rates, and excess adipose tissue is involved in respective pathologies. Here we established a human adipose tissue slice cultures (HATSC) model ex vivo. HATSC match the in vivo cell composition of human adipose tissue with, among others, mature adipocytes, mesenchymal stem cells as well as stroma tissue and immune cells. This is a new method, optimized for live imaging, to study adipose tissue and cell-based mechanisms of obesity in particular. HATSC survival was tested by means of conventional and immunofluorescence histological techniques, functional analyses and live imaging. Surgery-derived tissue was cut with a tissue chopper in 500 μm sections and transferred onto membranes building an air-liquid interface. HATSC were cultured in six-well plates filled with Dulbecco's Modified Eagle's Medium (DMEM), insulin, transferrin, and selenium, both with and without serum. After 0, 1, 7 and 14 days in vitro, slices were fixated and analyzed by morphology and Perilipin A for tissue viability. Immunofluorescent staining against IBA1, CD68 and Ki67 was performed to determine macrophage survival and proliferation. These experiments showed preservation of adipose tissue as well as survival and proliferation of monocytes and stroma tissue for at least 14 days in vitro even in the absence of serum. The physiological capabilities of adipocytes were functionally tested by insulin stimulation and measurement of Phospho-Akt on day 7 and 14 in vitro. Viability was further confirmed by live imaging using Calcein-AM (viable cells) and propidium iodide (apoptosis/necrosis). In conclusion, HATSC have been successfully established by preserving the monovacuolar form of adipocytes and surrounding macrophages and connective tissue. This model allows further analysis of mature human adipose tissue biology ex vivo.

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Transcriptional profiling identifies strain-specific effects of caloric restriction and opposite responses in human and mouse white adipose tissue

Cited by 9 publications

References 84 publications

Transcriptomic Effects of Healthspan-Promoting Dietary Interventions: Current Evidence and Future Directions

Transcriptomic Effects of Healthspan-Promoting Dietary Interventions: Current Evidence and Future Directions

Mouse background genetics in biomedical research: The devil's in the details

Examination of ex-vivo viability of human adipose tissue slice culture

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