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A Difference in Fatty Acid Composition of Isocaloric High-Fat Diets Alters Metabolic Flexibility in Male C57BL/6JOlaHsd Mice.

Duivenvoorde LP, van Schothorst EM, Swarts HM, Kuda O, Steenbergh E, Termeulen S, Kopecky J, Keijer J - PLoS ONE (2015)

Bottom Line: We found that the HFs diet, compared to the HFpu diet, increased mean adipocyte size, liver damage, and ectopic lipid storage in liver and muscle; although, we did not find differences in body weight, total adiposity, adipose tissue health, serum adipokines, whole body energy balance, or circadian rhythm between HFs and HFpu mice.To conclude, the HFs versus the HFpu diet increased ectopic fat storage, liver damage, and mean adipocyte size and reduced metabolic flexibility in male mice.This study underscores the physiological relevance of indirect calorimetry-based challenge tests.

View Article: PubMed Central - PubMed

Affiliation: Human and Animal Physiology, Wageningen University, Wageningen, The Netherlands.

ABSTRACT
Poly-unsaturated fatty acids (PUFAs) are considered to be healthier than saturated fatty acids (SFAs), but others postulate that especially the ratio of omega-6 to omega-3 PUFAs (n6/n3 ratio) determines health. Health can be determined with biomarkers, but functional health status is likely better reflected by challenge tests that assess metabolic flexibility. The aim of this study was to determine the effect of high-fat diets with different fatty acid compositions, but similar n6/n3 ratio, on metabolic flexibility. Therefore, adult male mice received isocaloric high-fat diets with either predominantly PUFAs (HFpu diet) or predominantly SFAs (HFs diet) but similar n6/n3 ratio for six months, during and after which several biomarkers for health were measured. Metabolic flexibility was assessed by the response to an oral glucose tolerance test, a fasting and re-feeding test and an oxygen restriction test (OxR; normobaric hypoxia). The latter two are non-invasive, indirect calorimetry-based tests that measure the adaptive capacity of the body as a whole. We found that the HFs diet, compared to the HFpu diet, increased mean adipocyte size, liver damage, and ectopic lipid storage in liver and muscle; although, we did not find differences in body weight, total adiposity, adipose tissue health, serum adipokines, whole body energy balance, or circadian rhythm between HFs and HFpu mice. HFs mice were, furthermore, less flexible in their response to both fasting- re-feeding and OxR, while glucose tolerance was indistinguishable. To conclude, the HFs versus the HFpu diet increased ectopic fat storage, liver damage, and mean adipocyte size and reduced metabolic flexibility in male mice. This study underscores the physiological relevance of indirect calorimetry-based challenge tests.

No MeSH data available.


Related in: MedlinePlus

RER during the OxR challenge after 25 weeks of HF feeding.HFpu and HFs mice were fasted and exposed to normoxic air (A; 20.8% O2) or to oxygen restriction (B; 12.0% O2) for 6 hours. Asterisks (in B) indicate the individual time points at which the 2-way ANOVA post-hoc analysis revealed significant differences between HFpu and HFs mice. RER values of individual mice were averaged during the 6 hours in normal or hypoxic air (C) and used to estimate the percentage of energy (en%) from glucose oxidation (D). Blood glucose was measured directly after the exposure to OxR or normal air (E). * P<0.05 and ** P< 0.01 HFs mice vs. HFpu mice.
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pone.0128515.g005: RER during the OxR challenge after 25 weeks of HF feeding.HFpu and HFs mice were fasted and exposed to normoxic air (A; 20.8% O2) or to oxygen restriction (B; 12.0% O2) for 6 hours. Asterisks (in B) indicate the individual time points at which the 2-way ANOVA post-hoc analysis revealed significant differences between HFpu and HFs mice. RER values of individual mice were averaged during the 6 hours in normal or hypoxic air (C) and used to estimate the percentage of energy (en%) from glucose oxidation (D). Blood glucose was measured directly after the exposure to OxR or normal air (E). * P<0.05 and ** P< 0.01 HFs mice vs. HFpu mice.

Mentions: Finally, metabolic flexibility was assessed using an exposure to OxR. HFpu and HFs mice did not differ in RER under normoxic conditions (Fig 5A). Exposure to OxR increased RER in HFpu mice compared to HFs mice (Fig 5B and 5C), which translates to an increase in the percentage of energy from glucose oxidation (Fig 5D). An increase in glucose oxidation is considered advantageous during OxR since the oxidation of glucose requires less oxygen than the oxidation of an equimolar amount of fat. Furthermore, an increase in glucose oxidation can prevent the increase in blood glucose levels that is often seen during OxR [9]. The analysis of blood glucose levels before and after exposure to OxR revealed a (statistical) interaction between the diet (HFpu and HFs) and oxygen level (OxR and normoxia) because HFpu and HFs responded differently to the exposure. Bonferroni post-hoc analysis revealed that HFs mice had higher blood glucose levels during OxR compared to HFpu mice (Fig 5E).


A Difference in Fatty Acid Composition of Isocaloric High-Fat Diets Alters Metabolic Flexibility in Male C57BL/6JOlaHsd Mice.

Duivenvoorde LP, van Schothorst EM, Swarts HM, Kuda O, Steenbergh E, Termeulen S, Kopecky J, Keijer J - PLoS ONE (2015)

RER during the OxR challenge after 25 weeks of HF feeding.HFpu and HFs mice were fasted and exposed to normoxic air (A; 20.8% O2) or to oxygen restriction (B; 12.0% O2) for 6 hours. Asterisks (in B) indicate the individual time points at which the 2-way ANOVA post-hoc analysis revealed significant differences between HFpu and HFs mice. RER values of individual mice were averaged during the 6 hours in normal or hypoxic air (C) and used to estimate the percentage of energy (en%) from glucose oxidation (D). Blood glucose was measured directly after the exposure to OxR or normal air (E). * P<0.05 and ** P< 0.01 HFs mice vs. HFpu mice.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4476692&req=5

pone.0128515.g005: RER during the OxR challenge after 25 weeks of HF feeding.HFpu and HFs mice were fasted and exposed to normoxic air (A; 20.8% O2) or to oxygen restriction (B; 12.0% O2) for 6 hours. Asterisks (in B) indicate the individual time points at which the 2-way ANOVA post-hoc analysis revealed significant differences between HFpu and HFs mice. RER values of individual mice were averaged during the 6 hours in normal or hypoxic air (C) and used to estimate the percentage of energy (en%) from glucose oxidation (D). Blood glucose was measured directly after the exposure to OxR or normal air (E). * P<0.05 and ** P< 0.01 HFs mice vs. HFpu mice.
Mentions: Finally, metabolic flexibility was assessed using an exposure to OxR. HFpu and HFs mice did not differ in RER under normoxic conditions (Fig 5A). Exposure to OxR increased RER in HFpu mice compared to HFs mice (Fig 5B and 5C), which translates to an increase in the percentage of energy from glucose oxidation (Fig 5D). An increase in glucose oxidation is considered advantageous during OxR since the oxidation of glucose requires less oxygen than the oxidation of an equimolar amount of fat. Furthermore, an increase in glucose oxidation can prevent the increase in blood glucose levels that is often seen during OxR [9]. The analysis of blood glucose levels before and after exposure to OxR revealed a (statistical) interaction between the diet (HFpu and HFs) and oxygen level (OxR and normoxia) because HFpu and HFs responded differently to the exposure. Bonferroni post-hoc analysis revealed that HFs mice had higher blood glucose levels during OxR compared to HFpu mice (Fig 5E).

Bottom Line: We found that the HFs diet, compared to the HFpu diet, increased mean adipocyte size, liver damage, and ectopic lipid storage in liver and muscle; although, we did not find differences in body weight, total adiposity, adipose tissue health, serum adipokines, whole body energy balance, or circadian rhythm between HFs and HFpu mice.To conclude, the HFs versus the HFpu diet increased ectopic fat storage, liver damage, and mean adipocyte size and reduced metabolic flexibility in male mice.This study underscores the physiological relevance of indirect calorimetry-based challenge tests.

View Article: PubMed Central - PubMed

Affiliation: Human and Animal Physiology, Wageningen University, Wageningen, The Netherlands.

ABSTRACT
Poly-unsaturated fatty acids (PUFAs) are considered to be healthier than saturated fatty acids (SFAs), but others postulate that especially the ratio of omega-6 to omega-3 PUFAs (n6/n3 ratio) determines health. Health can be determined with biomarkers, but functional health status is likely better reflected by challenge tests that assess metabolic flexibility. The aim of this study was to determine the effect of high-fat diets with different fatty acid compositions, but similar n6/n3 ratio, on metabolic flexibility. Therefore, adult male mice received isocaloric high-fat diets with either predominantly PUFAs (HFpu diet) or predominantly SFAs (HFs diet) but similar n6/n3 ratio for six months, during and after which several biomarkers for health were measured. Metabolic flexibility was assessed by the response to an oral glucose tolerance test, a fasting and re-feeding test and an oxygen restriction test (OxR; normobaric hypoxia). The latter two are non-invasive, indirect calorimetry-based tests that measure the adaptive capacity of the body as a whole. We found that the HFs diet, compared to the HFpu diet, increased mean adipocyte size, liver damage, and ectopic lipid storage in liver and muscle; although, we did not find differences in body weight, total adiposity, adipose tissue health, serum adipokines, whole body energy balance, or circadian rhythm between HFs and HFpu mice. HFs mice were, furthermore, less flexible in their response to both fasting- re-feeding and OxR, while glucose tolerance was indistinguishable. To conclude, the HFs versus the HFpu diet increased ectopic fat storage, liver damage, and mean adipocyte size and reduced metabolic flexibility in male mice. This study underscores the physiological relevance of indirect calorimetry-based challenge tests.

No MeSH data available.


Related in: MedlinePlus