Human skeletal muscle metabolic responses to 6 days of high‐fat overfeeding are associated with dietary n‐3PUFA content and muscle oxidative capacity

Abstract

Understanding human physiological responses to high‐fat energy excess (HFEE) may help combat the development of metabolic disease. We aimed to investigate the impact of manipulating the n‐3PUFA content of HFEE diets on whole‐body and skeletal muscle markers of insulin sensitivity. Twenty healthy males were overfed (150% energy, 60% fat, 25% carbohydrate, 15% protein) for 6 d. One group (n = 10) received 10% of fat intake as n‐3PUFA rich fish oil (HF‐FO), and the other group consumed a mix of fats (HF‐C). Oral glucose tolerance tests with stable isotope tracer infusions were conducted before, and following, HFEE, with muscle biopsies obtained in basal and insulin‐stimulated states for measurement of membrane phospholipids, ceramides, mitochondrial enzyme activities, and PKB and AMPKα2 activity. Insulin sensitivity and glucose disposal did not change following HFEE, irrespective of group. Skeletal muscle ceramide content increased following HFEE (8.5 ± 1.2 to 12.1 ± 1.7 nmol/mg, p = .03), irrespective of group. No change in mitochondrial enzyme activity was observed following HFEE, but citrate synthase activity was inversely associated with the increase in the ceramide content (r=−0.52, p = .048). A time by group interaction was observed for PKB activity (p = .003), with increased activity following HFEE in HF‐C (4.5 ± 13.0mU/mg) and decreased activity in HF‐FO (−10.1 ± 20.7 mU/mg) following HFEE. Basal AMPKα2 activity increased in HF‐FO (4.1 ± 0.6 to 5.3 ± 0.7mU/mg, p = .049), but did not change in HF‐C (4.6 ± 0.7 to 3.8 ± 0.9mU/mg) following HFEE. We conclude that early skeletal muscle signaling responses to HFEE appear to be modified by dietary n‐3PUFA content, but the potential impact on future development of metabolic disease needs exploring.

In Vivo and In Vitro Quantification of Glucose Kinetics: From Bedside to Bench

“…In other words, the faster the tracee turnover, the lower the E p for a given F . The tracer dilution model can be applicable to assessments of in vivo kinetics of various metabolites including amino acids [ 26 , 44 – 46 ], palmitate [ 6 , 47 , 48 ], glycerol [ 49 – 51 ], pyruvate [ 52 ], lactate [ 53 – 55 ] as well as glucose [ 8 , 11 , 56 , 57 ] in steady states and non-steady states.…”

“…Unlike steady state conditions, it is more complex to calculate tracee kinetics in non-steady state conditions such as after meal intake [ 8 , 11 , 56 ] and during exercise [ 3 , 4 ], as both the pool size and tracer enrichment of glucose are changing. In this section, we will discuss how to calculate non-steady state glucose kinetics using an example of an OGTT condition [ 8 , 11 , 56 ]. To determine non-steady state glucose kinetics, dual glucose tracers are typically used: one for IV infusion and the other for an oral glucose challenge (e.g., 75 g glucose consisting of 3.75 g labeled glucose and 71.25 g unlabeled glucose, giving an MPE of 5%).…”

“…Only a few grams of glucose (i.e., the plasma glucose pool size, 100 mg/dL blood or 3 g for a 70 kg healthy person with a plasma volume of 3 L) circulate in the blood, which supplies all the necessary fuels (i.e., glucose) to critical organs such as the brain. Accordingly, the maintenance of the infinitesimal size of this plasma glucose pool, a physiological priority, is typically stable in healthy individuals, even in perturbed situations such as during exercise [ 1 – 7 ] or after a meal intake [ 8 , 9 ]. For example, even following a 75 g glucose challenge (25 times the plasma pool size, similar to the amount of sugar contained in two regular Cokes), the plasma glucose concentrations typically do not rise above 200 mg/dL (<2-fold the pool size) and then return to the baseline within 2 hours in healthy individuals [ 8 , 10 ], as opposed to the insulin-resistant state [ 11 ] or diabetic conditions [ 12 , 13 ].…”

“…Accordingly, the maintenance of the infinitesimal size of this plasma glucose pool, a physiological priority, is typically stable in healthy individuals, even in perturbed situations such as during exercise [ 1 – 7 ] or after a meal intake [ 8 , 9 ]. For example, even following a 75 g glucose challenge (25 times the plasma pool size, similar to the amount of sugar contained in two regular Cokes), the plasma glucose concentrations typically do not rise above 200 mg/dL (<2-fold the pool size) and then return to the baseline within 2 hours in healthy individuals [ 8 , 10 ], as opposed to the insulin-resistant state [ 11 ] or diabetic conditions [ 12 , 13 ]. The tight regulation of blood glucose concentrations is achieved through the cooperative interplay among multiple organs including the brain, liver, pancreas, muscle, and adipose tissue at multiple levels of regulation [ 9 , 14 ].…”

Is vascular insulin resistance an early step in diet-induced whole-body insulin resistance?

“…No change with MCSFA 21% reduction in insulin sensitivity and 17% in glucose disposal as assessed via HEC in the LCSFA group. Not assessed Wardle et al [ 52 ] 6 days N = 10 M HCHF-C N = 10 M HCHF-FO HCHF 150% increase in TE Intervention HCHF-C: hyperenergetic ↑FAT diet (25% from CHO and 60% from FAT) Intervention HCHF-FO: hyperenergetic ↑FAT diet (25% from CHO and 60% from FAT [6% TE from fish oil]) Body weight increased by 0.5 kg in HCHF-C and 1 kg in HCHF-FO Not reported No difference in HOMA-IR. No change in Glu or Ins during OGTT.…”