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

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.

Effects of a wide range of dietary nicotinamide riboside (NR) concentrations on metabolic flexibility and white adipose tissue (WAT) of mice fed a mildly obesogenic diet

“…On the other hand, these parameters were not fully deteriorated as, for example, in Ob/Ob mice . Metabolic flexibility is a biomarker for metabolic health that can be assessed non‐invasively using indirect calorimetry . Using a fast‐refeeding challenge, we here found a dose‐response effect, showing that mice fed 30 mg NR/kg diet (30NR) were more metabolically flexible than the wide range of other NR concentrations.…”

“…The metabolic health effects of NR as an exclusive source of vitamin B3 at nutritional relevant levels are unknown. Recently, the ability to rapidly switch metabolism between carbohydrate oxidation and fatty acid oxidation, so‐called metabolic flexibility, has been recognized as a sensitive biomarker for metabolic health in nutritional interventions . Metabolic flexibility can be assessed by analysing the respiratory exchange ratio (RER) during a fast‐refeeding challenge in non‐invasive indirect calorimetry.…”

The Effect of a High-Fat Diet on the Fatty Acid Composition in the Hearts of Mice

“…Although there are some studies investigating the effects of dietary fat on rodent cardiac functions, most of them do not report specific FA profiles or do so only for total lipid FA profiles in heart tissue [50,53,72]. Alternatively, only FA profiles for one selected group of lipid species are presented [86][87][88]. Some studies focused mostly on SFAs and MUFAs [51], while PUFAs have not been widely reported.…”

No Adverse Programming by Post‐Weaning Dietary Fructose of Body Weight, Adiposity, Glucose Tolerance, or Metabolic Flexibility

“…In week 11, OGTT analyses were performed as previously published, with minor modifications. Briefly, food was removed 1 h after start of the light phase.…”