Tritrophic phenological match-mismatch in space and time

Increasing temperatures associated with climate change may generate phenological mismatches that disrupt previously synchronous trophic interactions. Most work on mismatch has focused on temporal trends, whereas spatial variation in the degree of trophic synchrony has largely been neglected, even though the degree to which mismatch varies in space has implications for meso-scale population dynamics and evolution. Here we quantify latitudinal trends in phenological mismatch, using phenological data on an oak–caterpillar–bird system from across the UK. Increasing latitude delays phenology of all species, but more so for oak, resulting in a shorter interval between leaf emergence and peak caterpillar biomass at northern locations. Asynchrony found between peak caterpillar biomass and peak nestling demand of blue tits, great tits and pied flycatchers increases in earlier (warm) springs. There is no evidence of spatial variation in the timing of peak nestling demand relative to peak caterpillar biomass for any species. Phenological mismatch alone is thus unlikely to explain spatial variation in population trends. Given projections of continued spring warming, we predict that temperate forest birds will become increasingly mismatched with peak caterpillar timing. Latitudinal invariance in the direction of mismatch may act as a double-edged sword that presents no opportunities for spatial buffering from the effects of mismatch on population size, but generates spatially consistent directional selection on timing, which could facilitate rapid evolutionary change

High-fat overfeeding impairs peripheral glucose metabolism and muscle microvascular eNOS Ser1177 phosphorylation.

CONTEXT: The mechanisms responsible for dietary fat-induced insulin resistance of skeletal muscle and its microvasculature are only partially understood. OBJECTIVE: To determine the impact of high-fat overfeeding on postprandial glucose fluxes, muscle insulin signaling, and muscle microvascular eNOS content and activation. DESIGN: Fifteen non-obese volunteers consumed a high-fat (64%) high-energy (+47%) diet for 7 days. Experiments were performed before and after the diet. Stable isotope tracers were used to determine glucose fluxes in response to carbohydrate plus protein ingestion. Muscle insulin signaling was determined as well as the content and activation state of muscle microvascular eNOS. RESULTS: High-fat overfeeding impaired postprandial glycemic control as demonstrated by higher concentrations of glucose (+11%; P = 0.004) and insulin (+19%; P = 0.035). Carbohydrate plus protein ingestion suppressed endogenous glucose production to a similar extent before and after the diet. Conversely, high-fat overfeeding reduced whole body glucose clearance (-16%; P = 0.021) and peripheral insulin sensitivity (-26%; P = 0.006). This occurred despite only minor alterations in skeletal muscle insulin signaling. High-fat overfeeding reduced eNOS content in terminal arterioles (P = 0.017) and abolished the increase in eNOS Ser1177 phosphorylation that was seen after carbohydrate plus protein ingestion. CONCLUSION: High-fat overfeeding impaired whole-body glycemic control due to reduced glucose clearance, not elevated endogenous glucose production. The finding that high-fat overfeeding abolished insulin-mediated eNOS Ser1177 phosphorylation in the terminal arterioles suggests that impairments in the vasodilatory capacity of the skeletal muscle microvasculature may contribute to early dietary fat-induced impairments in glycemic control

A 7-day high-fat, high-calorie diet induces fibre-specific increases in intramuscular triglyceride and perilipin protein expression in human skeletal muscle

KEY POINTS: We have recently shown that a high-fat high-calorie (HFHC) diet decreases whole body glucose clearance without impairing skeletal muscle insulin signalling, in healthy lean individuals. These diets are also known to increase skeletal muscle IMTG stores, but the effect on lipid metabolites leading to skeletal muscle insulin resistance has not been investigated. This study measured the effect of 7 days HFHC diet on: 1) skeletal muscle concentration of lipid metabolites, and 2) potential changes in the perilipin (PLIN) content of the lipid droplets (LD) storing IMTG. The HFHC diet increased PLIN3 protein expression and redistributed PLIN2 to LD stores in type I fibres. The HFHC diet increased IMTG content in type I fibres, while lipid metabolite concentrations remained the same. The data suggest that the increases in IMTG stores assists reducing the accumulation of lipid metabolites known to contribute to skeletal muscle insulin resistance. ABSTRACT: A HFHC diet reduces whole body glucose clearance without impairing skeletal muscle insulin signalling in healthy lean individuals. HFHC diets also increase skeletal muscle lipid stores. However, unlike certain lipid metabolites, intramuscular triglyceride (IMTG) stored within lipid droplets (LD) does not directly contribute to skeletal muscle insulin resistance. Increased expression of perilipin (PLIN) proteins and colocalisation to LD has been shown to assist in IMTG storage. We aimed to test the hypothesis that 7 days on a HFHC diet increases IMTG content while minimising accumulation of lipid metabolites known to disrupt skeletal muscle insulin signalling in sedentary and obese individuals. We also aimed to identify changes in expression and subcellular distribution of proteins involved in IMTG storage. Muscle biopsies were obtained from the m. vastus lateralis of 13 (n = 11 males, n = 2 females) healthy lean individuals (age: 23 ± 2.5 y, BMI: 24.5 ± 2.4 kg m-2 ), following an overnight fast, before and after consuming a high-fat (64% energy) high-calorie (+47% kcal) diet for 7 days. After the HFHC diet, IMTG content increased in type I fibres only (+10%; P < 0.001), whereas there was no change in the concentration of either total diacylglycerol (P = 0.123) or total ceramides (P = 0.150). Of the PLINs investigated, only PLIN3 content increased (+50%; P < 0.01) solely in type I fibres. LDs labelled with PLIN2 increased (80%; P < 0.01), also in type I fibres only. We propose that these adaptations to LD support IMTG storage and minimise accumulation of lipid metabolites to protect skeletal muscle insulin signalling following 7 days HFHC diet. This article is protected by copyright. All rights reserved

Divergence exists in the subcellular distribution of intramuscular triglyceride in human skeletal muscle dependent on the choice of lipid dye.

Despite over 50 years of research, a comprehensive understanding of how intramuscular triglyceride (IMTG) is stored in skeletal muscle and its contribution as a fuel during exercise is lacking. Immunohistochemical techniques provide information on IMTG content and lipid droplet (LD) morphology on a fibre type and subcellular-specific basis, and the lipid dye Oil Red O (ORO) is commonly used to achieve this. BODIPY 493/503 (BODIPY) is an alternative lipid dye with lower background staining and narrower emission spectra. Here we provide the first quantitative comparison of BODIPY and ORO for investigating exercise-induced changes in IMTG content and LD morphology on a fibre type and subcellular-specific basis. Estimates of IMTG content were greater when using BODIPY, which was predominantly due to BODIPY detecting a larger number of LDs, compared to ORO. The subcellular distribution of intramuscular lipid was also dependent on the lipid dye used; ORO detects a greater proportion of IMTG in the periphery (5 μm below cell membrane) of the fibre, whereas IMTG content was higher in the central region using BODIPY. In response to 60 min moderate-intensity cycling exercise, IMTG content was reduced in both the peripheral (- 24%) and central region (- 29%) of type I fibres (P < 0.05) using BODIPY, whereas using ORO, IMTG content was only reduced in the peripheral region of type I fibres (- 31%; P < 0.05). As well as highlighting some methodological considerations herein, our investigation demonstrates that important differences exist between BODIPY and ORO for detecting and quantifying IMTG on a fibre type and subcellular-specific basis

Young, healthy males and females present cardiometabolic protection against the detrimental effects of a 7-day high-fat high-calorie diet

Purpose: High-fat, high-calorie (HFHC) diets have been used as a model to investigate lipid-induced insulin resistance. Short-term HFHC diets reduce insulin sensitivity in young healthy males, but to date, no study has directly compared males and females to elucidate sex-specific differences in the effects of a HFHC diet on functional metabolic and cardiovascular outcomes. Methods: Eleven males (24 ± 4 years; BMI 23 ± 2 kg.m−2; V̇O2 peak 62.3 ± 8.7 ml.min−1.kg−1FFM) were matched to 10 females (25 ± 4 years; BMI 23 ± 2 kg.m−2; V̇O2 peak 58.2 ± 8.2 ml.min−1.kg−1FFM). Insulin sensitivity, measured via oral glucose tolerance test, metabolic flexibility, arterial stiffness, body composition and blood lipids and liver enzymes were measured before and after 7 days of a high-fat (65% energy) high-calorie (+ 50% kcal) diet. Results: The HFHC diet did not change measures of insulin sensitivity, metabolic flexibility or arterial stiffness in either sex. There was a trend towards increased total body fat mass (kg) after the HFHC diet (+ 1.8% and + 2.3% for males and females, respectively; P = 0.056). In contrast to females, males had a significant increase in trunk to leg fat mass ratio (+ 5.1%; P = 0.005). Conclusion: Lean, healthy young males and females appear to be protected from the negative cardio-metabolic effects of a 7-day HFHC diet. Future research should use a prolonged positive energy balance achieved via increased energy intake and reduced energy expenditure to exacerbate negative metabolic and cardiovascular functional outcomes to determine whether sex-specific differences exist under more metabolically challenging conditions

High intramuscular triglyceride turnover rates and the link to insulin sensitivity: Influence of obesity, type 2 diabetes and physical activity.

Large intramuscular triglyceride (IMTG) stores in sedentary, obese individuals have been linked to insulin resistance, yet well-trained athletes exhibit high IMTG levels whilst maintaining insulin sensitivity. Contrary to previous assumptions, it is now known that IMTG content per se does not result in insulin resistance. Rather, insulin resistance is caused, at least in part, by the presence of high concentrations of harmful lipid metabolites, such as diacylglycerols and ceramides in muscle. Several mechanistic differences between obese sedentary individuals and their highly-trained counterparts have been identified, that determine the differential capacity for IMTG synthesis and breakdown in these populations. In this review, we first describe the most up-to-date mechanisms by which a low IMTG turnover rate (both breakdown and synthesis) leads to the accumulation of lipid metabolites and results in skeletal muscle insulin resistance. We then explore current and potential exercise and nutritional strategies which target IMTG turnover in sedentary obese individuals, to improve insulin sensitivity. Overall, improving IMTG turnover should be an important component of successful interventions which aim to prevent the development of insulin resistance in the ever-expanding sedentary, overweight and obese populations. Novelty Bullet points • A description of the most up-to-date mechanisms regulating turnover of the IMTG pool. • An exploration of current and potential exercise/nutritional strategies to target and enhance IMTG turnover in obese individuals • Overall, highlights the importance of improving IMTG turnover to prevent the development of insulin resistance

Comprehensive interrogation of human skeletal muscle reveals a dissociation between insulin resistance and mitochondrial capacity

AbstractAims/HypothesisInsulin resistance and blunted mitochondrial capacity in skeletal muscle are often synonymous; however, this association remains controversial. The aim of this study was to perform an in-depth multi-factorial comparison of skeletal muscle mitochondrial capacity between individuals who were lean and active (Active), individuals with obesity (Obese) and individuals with Obesity, insulin resistance and type 2 diabetes (T2D).MethodsSkeletal muscle biopsies were obtained from theVastus Lateralisof individuals who were lean and active (Active- n = 9), individuals with obesity (Obese- n = 9) and individuals with obesity insulin resistance and T2D (T2D- n =22) in this cross-sectional design. Mitochondrial capacity was assessed byex vivomitochondrial respiration with fatty-acid and glycolytic supported protocols adjusted for mitochondrial content (mtDNA and citrate synthase activity). Supercomplex assembly was measured by BN-PAGE and immunoblot. TCA cycle intermediates were assessed with targeted metabolomics. Exploratory transcriptomics and DNA methylation analyses were performed to uncover molecular differences affecting mitochondrial function among the three groups.ResultsActive had greater mitochondrial capacity compared to both Obese and T2D forex vivomitochondrial respiration with fatty-acid and glycolytic supported protocols adjusted for mitochondrial content (P&lt; 0.05). Complex IV supercomplex assembley was greater in Active compared to Obese and T2D (P&lt; 0.05) whereas Complex I and III supercomplex assembly was greater in Active compared to T2D only (P&lt; 0.05). TCA cycle intermediates; citrate, succinate, fumarate and malate were all significantly greater in Active compared to Obese and T2D (P&lt; 0.05). Strikingly, Obese and T2D do not differ in any of the skeletal muscle mitochondrial measurements. Active had an upregulation of genes related to respiration/mitochondrial capacity compared to both Obese and T2D. Transcriptional differences between Obese and T2D were not driven by mitochondrial related process. Active had reduced methylation correlated with increased gene expression for important mitochondrial-related genes, includingATP5PDandMFN2.Conclusions/InterpretationsWe reveal no discernable differences in skeletal muscle mitochondrial content, mitochondrial capacity and mitochondrial molecular profiles between obese individuals with and without T2D that had comparable levels of confounding factors (BMI, age, aerobic capacity) that affect mitochondrial capacity. We highlight that lean, active individuals have enhanced skeletal muscle mitochondrial capacity that is also reflected at the level of DNA methylation and gene transcription. The collective observation of comparable muscle mitochondrial capacity in individuals with obesity and T2D (vs. individuals without T2D) underscores a dissociation from skeletal muscle insulin resistance.Clinical trial numberNCT0191110</jats:sec

A 7‐day high‐fat, high‐calorie diet induces fibre‐specific increases in intramuscular triglyceride and perilipin protein expression in human skeletal muscle

KEY POINTS: We have recently shown that a high-fat high-calorie (HFHC) diet decreases whole body glucose clearance without impairing skeletal muscle insulin signalling, in healthy lean individuals. These diets are also known to increase skeletal muscle IMTG stores, but the effect on lipid metabolites leading to skeletal muscle insulin resistance has not been investigated. This study measured the effect of 7 days HFHC diet on: 1) skeletal muscle concentration of lipid metabolites, and 2) potential changes in the perilipin (PLIN) content of the lipid droplets (LD) storing IMTG. The HFHC diet increased PLIN3 protein expression and redistributed PLIN2 to LD stores in type I fibres. The HFHC diet increased IMTG content in type I fibres, while lipid metabolite concentrations remained the same. The data suggest that the increases in IMTG stores assists reducing the accumulation of lipid metabolites known to contribute to skeletal muscle insulin resistance. ABSTRACT: A HFHC diet reduces whole body glucose clearance without impairing skeletal muscle insulin signalling in healthy lean individuals. HFHC diets also increase skeletal muscle lipid stores. However, unlike certain lipid metabolites, intramuscular triglyceride (IMTG) stored within lipid droplets (LD) does not directly contribute to skeletal muscle insulin resistance. Increased expression of perilipin (PLIN) proteins and colocalisation to LD has been shown to assist in IMTG storage. We aimed to test the hypothesis that 7 days on a HFHC diet increases IMTG content while minimising accumulation of lipid metabolites known to disrupt skeletal muscle insulin signalling in sedentary and obese individuals. We also aimed to identify changes in expression and subcellular distribution of proteins involved in IMTG storage. Muscle biopsies were obtained from the m. vastus lateralis of 13 (n = 11 males, n = 2 females) healthy lean individuals (age: 23 ± 2.5 y, BMI: 24.5 ± 2.4 kg m-2 ), following an overnight fast, before and after consuming a high-fat (64% energy) high-calorie (+47% kcal) diet for 7 days. After the HFHC diet, IMTG content increased in type I fibres only (+10%; P < 0.001), whereas there was no change in the concentration of either total diacylglycerol (P = 0.123) or total ceramides (P = 0.150). Of the PLINs investigated, only PLIN3 content increased (+50%; P < 0.01) solely in type I fibres. LDs labelled with PLIN2 increased (80%; P < 0.01), also in type I fibres only. We propose that these adaptations to LD support IMTG storage and minimise accumulation of lipid metabolites to protect skeletal muscle insulin signalling following 7 days HFHC diet