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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

Mean adipocyte size and prevalence of crown-like structures in eWAT after 27 weeks of HF feeding.Representative images (A) of the haematoxylin stainings that were used to determine the average adipocyte surface area (B) in eWAT of HFpu and HFs mice. The bar in each picture represents a distance of 100 μm. The number of CLS (C) was determined with a MAC-2 macrophage staining in eWAT. * P< 0.05 HFs mice vs. HFpu mice.
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pone.0128515.g002: Mean adipocyte size and prevalence of crown-like structures in eWAT after 27 weeks of HF feeding.Representative images (A) of the haematoxylin stainings that were used to determine the average adipocyte surface area (B) in eWAT of HFpu and HFs mice. The bar in each picture represents a distance of 100 μm. The number of CLS (C) was determined with a MAC-2 macrophage staining in eWAT. * P< 0.05 HFs mice vs. HFpu mice.

Mentions: Adipocytes in eWAT were significantly larger in HFs mice compared to HFpu mice (Fig 2A and 2B), whereas no difference in the number of crown-like structures in eWAT was observed (Fig 2C). HFs mice had significantly higher triacylglycerol levels in liver and muscle (Table 2), which indicates increased ectopic lipid storage. Consistently, serum aspartate transaminase and alanine transaminase levels, markers for liver damage, were both significantly increased in HFs mice compared with HFpu mice (Table 2). To obtain an impression of the extent of liver steatosis in week 27 compared to the situation at the start of the intervention, hepatic lipids were stained with Oil-red-O after either 5 days or 27 weeks of high-fat feeding in a limited number of mice per group (S1 Fig). Both the number and size of hepatic lipid droplets strongly increased over time.


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)

Mean adipocyte size and prevalence of crown-like structures in eWAT after 27 weeks of HF feeding.Representative images (A) of the haematoxylin stainings that were used to determine the average adipocyte surface area (B) in eWAT of HFpu and HFs mice. The bar in each picture represents a distance of 100 μm. The number of CLS (C) was determined with a MAC-2 macrophage staining in eWAT. * P< 0.05 HFs mice vs. HFpu mice.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0128515.g002: Mean adipocyte size and prevalence of crown-like structures in eWAT after 27 weeks of HF feeding.Representative images (A) of the haematoxylin stainings that were used to determine the average adipocyte surface area (B) in eWAT of HFpu and HFs mice. The bar in each picture represents a distance of 100 μm. The number of CLS (C) was determined with a MAC-2 macrophage staining in eWAT. * P< 0.05 HFs mice vs. HFpu mice.
Mentions: Adipocytes in eWAT were significantly larger in HFs mice compared to HFpu mice (Fig 2A and 2B), whereas no difference in the number of crown-like structures in eWAT was observed (Fig 2C). HFs mice had significantly higher triacylglycerol levels in liver and muscle (Table 2), which indicates increased ectopic lipid storage. Consistently, serum aspartate transaminase and alanine transaminase levels, markers for liver damage, were both significantly increased in HFs mice compared with HFpu mice (Table 2). To obtain an impression of the extent of liver steatosis in week 27 compared to the situation at the start of the intervention, hepatic lipids were stained with Oil-red-O after either 5 days or 27 weeks of high-fat feeding in a limited number of mice per group (S1 Fig). Both the number and size of hepatic lipid droplets strongly increased over time.

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