A nutritional memory impairs survival, transcriptional and metabolic response to dietary restriction in old mice

AbstractDietary restriction (DR) during adulthood can greatly extend lifespan and improve metabolic health in diverse species. However, whether DR in mammals is still effective when applied for the first time at old age remains elusive. Here, we conducted a late-life DR switch experiment employing 800 mice, by switching old animals from ad libitum (AL) to DR and vice versa. Strikingly, the switch from DR-to-AL acutely increased mortality, while the switch from AL-to-DR caused only a weak and gradual increase in survival, highlighting a memory of earlier nutrition. A significant association between fat preservation and survival response pointed to the white adipose tissue (WAT) as a potential memory source. Consistently, post-switch RNA-seq profiling in liver and WAT demonstrated that the transcriptional and metabolic program of chronic DR remained largely refractory to the AL-to-DR switch specifically in adipose tissue. Integration of lipidomics confirmed impaired membrane lipogenesis and limited mitochondrial copy number increase under late-life DR as functional consequences of this memory effect. Together, our results provide evidence for a nutritional memory as a limiting factor for DR-induced longevity and metabolic remodeling of WAT in mammals.

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Endocrine and Metabolic Signaling in Retroperitoneal White Adipose Tissue Remodeling during Cold Acclimation

Journal of Obesity ◽

10.1155/2013/937572 ◽

2013 ◽

Vol 2013 ◽

pp. 1-8 ◽

Cited By ~ 12

Author(s):

Aleksandra Jankovic ◽

Aleksandra Korac ◽

Biljana Buzadzic ◽

Vesna Otasevic ◽

Ana Stancic ◽

...

Keyword(s):

Adipose Tissue ◽

Cold Acclimation ◽

White Adipose Tissue ◽

Protein Level ◽

Metabolic Response ◽

Expression Profiles ◽

Hypoxia Inducible Factor ◽

Metabolic Remodeling ◽

Retroperitoneal White Adipose Tissue ◽

Adipose Tissue Remodeling

The expression profiles of adiponectin, resistin, 5′-AMP-activated protein kinaseα(AMPKα), hypoxia-inducible factor-1α(HIF-1α), and key enzymes of glucose and fatty acid metabolism and oxidative phosphorylation in rat retroperitoneal white adipose tissue (RpWAT) during 45-day cold acclimation were examined. After transient suppression on day 1, adiponectin protein level increased following sustained cold exposure. In parallel, on day 1, the protein level of HIF-1αwas strongly induced and AMPKαsuppressed, while afterwards the reverse was seen. What is more, after an initial decrease on day 1, a sequential increase in pyruvate dehydrogenase, acyl-CoA dehydrogenase, cytochromecoxidase, and ATP synthase and a decrease in acetyl-CoA carboxylase (from day 3) were observed. Similar to adiponectin, protein level of resistin showed a biphasic profile: it increased after days 1, 3, and 7 and decreased below the control after 21 days of cold-acclimation. In summary, the data suggest that adiponectin and resistin are important integrators of RpWAT metabolic response and roles it plays during cold acclimation. It seems that AMPKαmediate adiponectin effects on metabolic remodeling RpWAT during cold acclimation.

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The Effects of Thyroxine and Isopropylnoradrenaline on Cytochrome Oxidase Activity in Brown Adipose Tissue

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y73-114 ◽

1973 ◽

Vol 51 (10) ◽

pp. 751-758 ◽

Cited By ~ 26

Author(s):

H. M. C. Heick ◽

C. Vachon ◽

Mary Ann Kallai ◽

Nicole Bégin-Heick ◽

J. LeBlanc

Keyword(s):

Adipose Tissue ◽

Brown Adipose Tissue ◽

Protein Content ◽

Cytochrome Oxidase ◽

Cold Adaptation ◽

Metabolic Response ◽

Mitochondrial Enzymes ◽

Cold Adapted ◽

Brown Adipose ◽

Hormonal Treatments

Groups of animals were treated with injections of isopropylnoradrenaline, thyroxine, or both hormones together. The effects of these hormonal treatments on the size, protein content, and level of some mitochondrial enzymes, in particular the cytochrome oxidase, were determined and compared to the effect on these parameters produced by cold adaptation. The changes observed were correlated with the resistance of the animals to cold stress and with their metabolic response to injections of isopropylnoradrenaline. All treatments increased the size of the brown adipose tissue. Whereas thyroxine had little effect on the protein content and cytochrome oxidase, both isopropylnoradrenaline and cold adaptation produced increases in these parameters. It appears that the isopropylnoradrenaline-treated animals mimic more closely the cold-adapted animals than do those with thyroxine treatment. However, the isopropylnoradrenaline-treated animals are not as resistant to cold as the cold-adapted animals.

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Combined influence of dietary restriction and treadmill running on MCP-1 and the expression of oxidative stress-related mRNA in the adipose tissue in obese mice

The Journal of Exercise Nutrition and Biochemistry ◽

10.5717/jenb.2014.18.3.311 ◽

2014 ◽

Vol 18 (3) ◽

pp. 311-318 ◽

Cited By ~ 5

Author(s):

Nayoung Ahn ◽

Kijin Kim

Keyword(s):

Oxidative Stress ◽

Adipose Tissue ◽

Dietary Restriction ◽

Treadmill Running ◽

Obese Mice

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Effects of Nutrition/Diet on Brown Adipose Tissue in Humans: A Systematic Review and Meta-Analysis

Nutrients ◽

10.3390/nu12092752 ◽

2020 ◽

Vol 12 (9) ◽

pp. 2752

Author(s):

Kelsey A. Heenan ◽

Andres E. Carrillo ◽

Jacob L. Fulton ◽

Edward J. Ryan ◽

Jason R. Edsall ◽

...

Keyword(s):

Systematic Review ◽

Adipose Tissue ◽

Brown Adipose Tissue ◽

Metabolic Response ◽

Meta Analysis ◽

Standardized Uptake Value ◽

Cochrane Library ◽

Bat Activity ◽

Brown Adipose ◽

Single Meal

Background: Brown adipose tissue (BAT) provides a minor contribution to diet-induced thermogenesis (DIT)—the metabolic response to food consumption. Increased BAT activity is generally considered beneficial for mammalian metabolism and has been associated with favorable health outcomes. The aim of the current systematic review was to explore whether nutritional factors and/or diet affect human BAT activity. Methods: We searched PubMed Central, Embase and Cochrane Library (trials) to conduct this systematic review (PROSPERO protocol: CRD42018082323). Results: We included 24 eligible papers that studied a total of 2785 participants. We found no mean differences in standardized uptake value of BAT following a single meal or after 6 weeks of L-Arginine supplementation. Resting energy expenditure (REE), however, was increased following a single meal and after supplementation of capsinoid and catechin when compared to a control condition (Z = 2.41, p = 0.02; mean difference = 102.47 (95% CI = 19.28–185.67)). Conclusions: Human BAT activity was not significantly affected by nutrition/diet. Moreover, REE was only increased in response to a single meal, but it is unlikely that this was due to increased BAT activity. BAT activity assessments in response to the chronic effect of food should be considered along with other factors such as body composition and/or environmental temperature.

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SHORT-TERM DIETARY RESTRICTION RESCUES MICE FROM SEPSIS AND REDUCES INFLAMMATION IN ADIPOSE TISSUE

The Gerontologist ◽

10.1093/geront/gnw162.715 ◽

2016 ◽

Vol 56 (Suppl_3) ◽

pp. 183-183

Keyword(s):

Adipose Tissue ◽

Dietary Restriction ◽

Short Term

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Inhibition by Oxytetracycline of the Development of the Enhanced Response to Noradrenaline in Cold-Acclimated Rats: A New Approach to the Study of Nonshivering Thermogenesis

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y71-070 ◽

1971 ◽

Vol 49 (6) ◽

pp. 545-553 ◽

Cited By ~ 10

Author(s):

Jean Himms–Hagen

Keyword(s):

Skeletal Muscle ◽

Adipose Tissue ◽

Brown Adipose Tissue ◽

Cytochrome Oxidase ◽

Oxidase Activity ◽

Metabolic Response ◽

Inner Membrane ◽

Cytochrome Oxidase Activity ◽

Mitochondrial Inner Membrane ◽

Brown Adipose

The aim of these experiments was to depress the increased metabolic activity of the brown adipose tissue in the intact rat during acclimation to cold in order to elucidate further the possible thermogenic and endocrine functions of this tissue. The antibiotic oxytetracycline was administered twice daily for 2 weeks to rats living at 4 °C in an attempt to inhibit the proliferation of mitochondria and of mitochondrial inner membrane known to occur in the brown adipose tissue in response to cold; control rats received saline during the same period. Total cytochrome oxidase activity served as an index of the amount of mitochondrial inner membrane in brown adipose tissue, liver, and skeletal muscle. The development of an enhanced calorigenic response to intravenously infused noradrenaline served as an index of the extent of acclimation to cold.Treatment with oxytetracycline inhibited both the cold-induced increase in cytochrome oxidase activity in brown adipose tissue and the cold-induced development of an enhanced calorigenic response to noradrenaline in the intact rats; a direct correlation was noted between the amount of cytochrome oxidase in brown adipose tissue and the size of the metabolic response to noradrenaline of the intact animals. However, the amount of oxygen that could be consumed by the total cytochrome oxidase in the brown adipose tissue was itself too small to account for the increase in oxygen consumption by the rat. Treatment of the rats with oxytetracycline did not alter the cold-induced growth of brown adipose tissue (as judged by the increase in wet weight and the increase in total protein); it also did not alter the cytochrome oxidase activities of liver or skeletal muscle. The effect of oxytetracycline seems, therefore, to be fairly specific for the mitochondria of the most rapidly dividing tissue, the brown adipose tissue. The conclusion is drawn that a protein synthesized in the mitochondria of the brown adipose tissue in response to cold is essential for adaptation to cold.

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