The Ratio of Linoleic and Linolenic Acid in the Pre-hibernation Diet Influences NFκB Signaling in Garden Dormice During Torpor

Logan, Samantha M.; Watts, A.; Posautz, Annika; Kübber‐Heiss, Anna; Painer, Johanna; Stalder, Gabrielle; Giroud, Sylvain; Storey, Kenneth B.

doi:10.3389/fmolb.2020.00097

Cited by 5 publications

(17 citation statements)

References 54 publications

(71 reference statements)

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“…For instance, increased levels of PGC-1α during hibernation in garden dormouse fed a high LA (or low ALA) diet could lead to co-activation of either PPARα or PPARγ, downstream activation of the mitochondrial transcription factor A (TFAM) and increased transcription of uncoupling protein-1 (UCP1); ultimately these changes would confer a more robust thermogenic capacity in animals fed a high LA (or low ALA) diet. This result is in line with finding from Logan et al (2020) reporting increased levels of anti-oxidative and anti-apoptotic factors in the same dormice fed a high LA (or low ALA) diet compared to low or intermediate LA (or high or intermediate ALA) dietary levels during hibernation (euthermia). Further, PGC-1α in cooperation with PPARα, can increase PRD1-BF1-RIZ1 homologous domain-containing 16 (PRDM16) transcription, essential for the development and maintenance of “beige”-adipose tissue within WAT ( Hondares et al, 2011 ; Ohno et al, 2012 ).…”

Section: Discussionsupporting

confidence: 92%

“…The fatty acid composition of the diets is summarized in Logan et al (2020) . During the fattening phase, dormice were fed one of the three specific diets, each differing in its lipid composition, made by adding either a 10% w/w of linseed oil as the source of n-3 fatty acids (notably ALA 18:3 n-3), or a 10% w/w of safflower oil as the source of n-6 fatty acids (mainly LA 18:2 n-6), or adding a 5% w/w of linseed oil and a 5% w/w of safflower oil to pellets the animals were accustomed to (Topix, Saturn Petcare GmbH, Bremen, Germany).…”

Section: Methodsmentioning

confidence: 99%

“…We used linear mixed-effects models (R package ‘nlme’) ( Pinheiro et al, 2014 ) with animal ID as random factor to test effects of dietary treatment (low, intermediate and high LA) and time (pre-hibernation vs. mid-hibernation) on WAT fatty acid composition. We reused previously published data of WAT fatty acid composition at pre-hibernation from Logan et al (2020) into the analyses to compare changes in fatty acid composition during the experimental hibernation period. All p -values from linear mixed-effects models were adjusted for multi-comparisons between fatty acid proportions using False Discovery Rate ( Benjamini and Hochberg, 1995 ).…”

Section: Methodsmentioning

confidence: 99%

“…Values are means from four analyses per diet. Data were extracted from Table 1 in Logan et al (2020).…”

Section: Dietsmentioning

confidence: 99%

“…Specifically, DNA binding activity of PPARs (PPARα, δ, and γ) were assessed in conjunction with total protein levels of the cofactor PGC1-α and downstream effector protein, liver-FABP (L-FABP). Altering the lipid composition of the GD’s pre-hibernation diet has been shown to change the molecular phenotype displayed during hibernation in mammals ( Logan et al, 2020 ), making it likely that molecular changes in fatty acid metabolism pathways will result from this difference.…”

Section: Introductionmentioning

confidence: 99%

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Regulation of Peroxisome Proliferator-Activated Receptor Pathway During Torpor in the Garden Dormouse, Eliomys quercinus

et al. 2020

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Differential levels of n-6 and n-3 essential polyunsaturated fatty acids (PUFAs) are incorporated into the hibernator’s diet in the fall season preceding prolonged, multi-days bouts of torpor, known as hibernation. Peroxisome proliferator-activated receptor (PPAR) transcriptional activators bind lipids and regulate genes involved in fatty acid transport, beta-oxidation, ketogenesis, and insulin sensitivity; essential processes for survival during torpor. Thus, the DNA-binding activity of PPARα, PPARδ, PPARγ, as well as the levels of PPARγ coactivator 1α (PGC-1α) and L-fatty acid binding protein (L-FABP) were investigated in the hibernating garden dormouse (Eliomys quercinus). We found that dormice were hibernating in a similar way regardless of the n-6/n-3 PUFA diets fed to the animals during the fattening phase prior to hibernation. Further, metabolic rates and body mass loss during hibernation did not differ between dietary groups, despite marked differences in fatty acid profiles observed in white adipose tissue prior and at mid-hibernation. Overall, maintenance of PPAR DNA-binding activity was observed during torpor, and across three n-6/n-3 ratios, suggesting alternate mechanisms for the prioritization of lipid catabolism during torpor. Additionally, while no change was seen in L-FABP, significantly altered levels of PGC-1α were observed within the white adipose tissue and likely contributes to enhanced lipid metabolism when the diet favors n-6 PUFAs, i.e., high n-6/n-3 ratio, in both the torpid and euthermic state. Altogether, the maintenance of lipid metabolism during torpor makes it likely that consistent activity or levels of the investigated proteins are in aid of this metabolic profile.

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Section: Discussionsupporting

confidence: 92%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

“…Values are means from four analyses per diet. Data were extracted from Table 1 in Logan et al (2020).…”

Section: Dietsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Regulation of Peroxisome Proliferator-Activated Receptor Pathway During Torpor in the Garden Dormouse, Eliomys quercinus

et al. 2020

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Translating PUFA omega 6:3 ratios from wild to captive hibernators (Urocitellus parryii) enhances sex-dependent mass-gain without increasing physiological stress indicators

et al. 2022

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Omega 3 polyunsaturated fatty acids (PUFAs) are well-documented for their influence on health and weight loss. Recent studies indicate omega 3 PUFAs may exert a negative impact on cellular stress and physiology in some hibernators. We asked if physiological stress indicators, lipid peroxidation and mass gain in Arctic Ground Squirrels (AGS) were negatively influenced by naturally occurring dietary omega 3 PUFA levels compared to omega 3 PUFA levels found in common laboratory diets. We found plasma fatty acid profiles of free-ranging AGS to be high in omega 3 PUFAs with balanced omega 6:3 ratios, while standard laboratory diets and plasma of captive AGS are high in omega 6 and low in omega 3 PUFAs with higher omega 6:3 ratios. Subsequently, we designed a diet to mimick free-range AGS omega 6:3 ratios in captive AGS. Groups of wild-caught juvenile AGS were either fed: (1) Mazuri Rodent Chow (Standard Rodent chow, 4.95 omega 6:3 ratio), or (2) balanced omega 6:3 chow (Balanced Diet, 1.38 omega 6:3). AGS fed the Balanced Diet had plasma omega 6:3 ratios that mimicked plasma profiles of wild AGS. Balanced Diet increased female body mass before hibernation, but did not influence levels of cortisol in plasma or levels of the lipid peroxidation product 4-HNE in brown adipose tissue. Overall, as the mass gain is critical during pre-hibernation for obligate hibernators, the results show that mimicking a fatty acid profile of wild AGS facilitates sex-dependent mass accumulation without increasing stress indicators.

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Elevated plasma phospholipid n-3 docosapentaenoic acid concentrations during hibernation

Strandvik¹,

Qureshi²,

Painer³

et al. 2023

PLoS ONE

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Factors for initiating hibernation are unknown, but the condition shares some metabolic similarities with consciousness/sleep, which has been associated with n-3 fatty acids in humans. We investigated plasma phospholipid fatty acid profiles during hibernation and summer in free-ranging brown bears (Ursus arctos) and in captive garden dormice (Eliomys quercinus) contrasting in their hibernation patterns. The dormice received three different dietary fatty acid concentrations of linoleic acid (LA) (19%, 36% and 53%), with correspondingly decreased alpha-linolenic acid (ALA) (32%, 17% and 1.4%). Saturated and monounsaturated fatty acids showed small differences between summer and hibernation in both species. The dormice diet influenced n-6 fatty acids and eicosapentaenoic acid (EPA) concentrations in plasma phospholipids. Consistent differences between summer and hibernation in bears and dormice were decreased ALA and EPA and marked increase of n-3 docosapentaenoic acid and a minor increase of docosahexaenoic acid in parallel with several hundred percent increase of the activity index of elongase ELOVL2 transforming C20-22 fatty acids. The highest LA supply was unexpectantly associated with the highest transformation of the n-3 fatty acids. Similar fatty acid patterns in two contrasting hibernating species indicates a link to the hibernation phenotype and requires further studies in relation to consciousness and metabolism.

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The Ratio of Linoleic and Linolenic Acid in the Pre-hibernation Diet Influences NFκB Signaling in Garden Dormice During Torpor

Cited by 5 publications

References 54 publications

Regulation of Peroxisome Proliferator-Activated Receptor Pathway During Torpor in the Garden Dormouse, Eliomys quercinus

Regulation of Peroxisome Proliferator-Activated Receptor Pathway During Torpor in the Garden Dormouse, Eliomys quercinus

Translating PUFA omega 6:3 ratios from wild to captive hibernators (Urocitellus parryii) enhances sex-dependent mass-gain without increasing physiological stress indicators

Elevated plasma phospholipid n-3 docosapentaenoic acid concentrations during hibernation

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