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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 fasting and re-feeding challenge after 25 weeks of HF feeding.HFpu and HFs mice were fasted and regained ad-libitum access to their feed at 14.00h, while RER was monitored continuously (A, the grey bars below the figure indicate the dark phase). RER values of individual mice were averaged when mice were fasting (from 23.00h to 6.00h), when mice were in a fasted state (from 6.00h to 14.00h) and during re-feeding (from 14.00h to 22.00h) (B). The table (C) summarises the maximal RER-value during re-feeding based on three consecutive measures, the food quotients of the diets, and the feed intake during the 8 hours of re-feeding. ** P< 0.01 HFs mice vs. HFpu mice.
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pone.0128515.g004: RER during the fasting and re-feeding challenge after 25 weeks of HF feeding.HFpu and HFs mice were fasted and regained ad-libitum access to their feed at 14.00h, while RER was monitored continuously (A, the grey bars below the figure indicate the dark phase). RER values of individual mice were averaged when mice were fasting (from 23.00h to 6.00h), when mice were in a fasted state (from 6.00h to 14.00h) and during re-feeding (from 14.00h to 22.00h) (B). The table (C) summarises the maximal RER-value during re-feeding based on three consecutive measures, the food quotients of the diets, and the feed intake during the 8 hours of re-feeding. ** P< 0.01 HFs mice vs. HFpu mice.

Mentions: Metabolic flexibility was also assessed with a fasting and re-feeding test. HFpu and HFs mice had low RER values when fasted, which indicates preferential whole body fat oxidation. During re-feeding, RER increased, which indicates a combination of both fat and carbohydrate oxidation on whole body level (Fig 4A). HFpu and HFs mice did not differ in mean RER during fasting (from 23.00h to 6.00h) or when they were in a fasted state (from 6.00h to 14.00h). During re-feeding (from 14.00h to 22.00h), however, HFpu mice showed a significantly larger increase in RER compared to HFs mice. Furthermore, the average RER over the complete period of re-feeding (Fig 4B) and maximal RER-value during re-feeding (Fig 4C) of HFpu mice matched the food quotient of the HFpu diet, which indicates that HFpu mice effectively alter their metabolism to use the nutrients that are available in the diet. In contrast, HFs mice did not increase RER levels above 0.815, which is significantly lower than the levels that were obtained in HFpu mice and is remarkably lower than the food quotient of the HFs diet. During re-feeding, mice had ad-libitum access to feed, during which HFpu and HFs mice consumed a similar amount of feed (Fig 4C).


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 fasting and re-feeding challenge after 25 weeks of HF feeding.HFpu and HFs mice were fasted and regained ad-libitum access to their feed at 14.00h, while RER was monitored continuously (A, the grey bars below the figure indicate the dark phase). RER values of individual mice were averaged when mice were fasting (from 23.00h to 6.00h), when mice were in a fasted state (from 6.00h to 14.00h) and during re-feeding (from 14.00h to 22.00h) (B). The table (C) summarises the maximal RER-value during re-feeding based on three consecutive measures, the food quotients of the diets, and the feed intake during the 8 hours of re-feeding. ** P< 0.01 HFs mice vs. HFpu mice.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4476692&req=5

pone.0128515.g004: RER during the fasting and re-feeding challenge after 25 weeks of HF feeding.HFpu and HFs mice were fasted and regained ad-libitum access to their feed at 14.00h, while RER was monitored continuously (A, the grey bars below the figure indicate the dark phase). RER values of individual mice were averaged when mice were fasting (from 23.00h to 6.00h), when mice were in a fasted state (from 6.00h to 14.00h) and during re-feeding (from 14.00h to 22.00h) (B). The table (C) summarises the maximal RER-value during re-feeding based on three consecutive measures, the food quotients of the diets, and the feed intake during the 8 hours of re-feeding. ** P< 0.01 HFs mice vs. HFpu mice.
Mentions: Metabolic flexibility was also assessed with a fasting and re-feeding test. HFpu and HFs mice had low RER values when fasted, which indicates preferential whole body fat oxidation. During re-feeding, RER increased, which indicates a combination of both fat and carbohydrate oxidation on whole body level (Fig 4A). HFpu and HFs mice did not differ in mean RER during fasting (from 23.00h to 6.00h) or when they were in a fasted state (from 6.00h to 14.00h). During re-feeding (from 14.00h to 22.00h), however, HFpu mice showed a significantly larger increase in RER compared to HFs mice. Furthermore, the average RER over the complete period of re-feeding (Fig 4B) and maximal RER-value during re-feeding (Fig 4C) of HFpu mice matched the food quotient of the HFpu diet, which indicates that HFpu mice effectively alter their metabolism to use the nutrients that are available in the diet. In contrast, HFs mice did not increase RER levels above 0.815, which is significantly lower than the levels that were obtained in HFpu mice and is remarkably lower than the food quotient of the HFs diet. During re-feeding, mice had ad-libitum access to feed, during which HFpu and HFs mice consumed a similar amount of feed (Fig 4C).

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