Altered Skeletal Muscle Fatty Acid Handling in Subjects with Impaired Glucose Tolerance as Compared to Impaired Fasting Glucose

Goossens, Gijs H.; Moors, C.C.M.; Jocken, Johan W. E.; Zijl, N.J. van der; Jans, Anneke; Konings, Ellen; Diamant, Michaëla; Blaak, Ellen E.

doi:10.3390/nu8030164

Cited by 22 publications

(33 citation statements)

References 37 publications

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“…Indeed, in the different prediabetic phenotypes the state of impaired glucose tolerance may be characterised by more pronounced peripheral or muscle IR, whilst the state of impaired fasting glucose by more pronounced hepatic IR (12) . Consistent with this, we previously showed that skeletal muscle lipid handling was disturbed in the impaired glucose tolerance state, characterised by an impaired postprandial insulin sensitivity, an increased postprandial TAG extraction and a reduced muscle lipid turnover, compared with individuals with impaired fasting glucose (13,14) .…”

Section: The Concept Of Tissue-specific Insulin Resistancesupporting

confidence: 75%

Current metabolic perspective on malnutrition in obesity: towards more subgroup-based nutritional approaches?

Blaak

2020

Proc. Nutr. Soc.

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Lifestyle intervention may be effective in reducing type 2 diabetes mellitus incidence and cardiometabolic risk. A more personalised nutritional approach based on an individual or subgroup-based metabolic profile may optimise intervention outcome. Whole body insulin resistance (IR) reflects defective insulin action in tissues such as muscle, liver, adipose tissue, gut and brain, which may precede the development of cardiometabolic diseases. IR may develop in different organs but the severity may vary between organs. Individuals with more pronounced hepatic IR have a distinct plasma metabolome and lipidome profile as compared with individuals with more pronounced muscle IR. Additionally, genes related to extracellular modelling were upregulated in abdominal subcutaneous adipose tissue in individuals with more pronounced hepatic IR, whilst genes related to inflammation as well as systemic low-grade inflammation were upregulated in individuals with primarily muscle IR. There are indications that these distinct IR phenotypes may also respond differentially to dietary macronutrient composition. Besides metabolic phenotype, microbial phenotype may be of importance in personalising the response to diet. In particular fibres or fibre mixtures, leading to a high distal acetate and SCFA production may have more pronounced effects on metabolic health. Notably, individuals with prediabetes may have a reduced response to diet-induced microbiota modulation with respect to host insulin sensitivity and metabolic health outcomes. Overall, we need more research to relate metabolic subphenotypes to intervention outcomes to define more optimal diets for individuals with or predisposed to chronic metabolic diseases.

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Section: The Concept Of Tissue-specific Insulin Resistancesupporting

confidence: 75%

Current metabolic perspective on malnutrition in obesity: towards more subgroup-based nutritional approaches?

Blaak

2020

Proc. Nutr. Soc.

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“…Despite slightly elevated plasma NEFA concentrations in T2DM as compared to healthy control subjects, a similar postprandial NEFA uptake in skeletal muscle was observed in both groups ( 32 ). Likewise, we have recently demonstrated a comparable skeletal muscle uptake of circulating NEFA in overweight and obese subjects with mild vs. more severe IR ( 33 ). Elevated plasma NEFA levels may, however, lead to increased uptake of NEFA into the liver ( 34 ).…”

Section: Ectopic Fat and Insulin Resistance: Pathophysiology And Intementioning

confidence: 70%

Ectopic Fat Accumulation in Distinct Insulin Resistant Phenotypes; Targets for Personalized Nutritional Interventions

et al. 2018

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Cardiometabolic diseases are one of the leading causes for disability and mortality in the Western world. The prevalence of these chronic diseases is expected to rise even further in the next decades. Insulin resistance (IR) and related metabolic disturbances are linked to ectopic fat deposition, which is the storage of excess lipids in metabolic organs such as liver and muscle. Notably, a vicious circle exists between IR and ectopic fat, together increasing the risk for the development of cardiometabolic diseases. Nutrition is a key-determining factor for both IR and ectopic fat deposition. The macronutrient composition of the diet may impact metabolic processes related to ectopic fat accumulation and IR. Interestingly, however, the metabolic phenotype of an individual may determine the response to a certain diet. Therefore, population-based nutritional interventions may not always lead to the most optimal (cardiometabolic) outcomes at the individual level, and differences in the metabolic phenotype may underlie conflicting findings related to IR and ectopic fat in dietary intervention studies. Detailed metabolic phenotyping will help to better understand the complex relationship between diet and metabolic regulation, and to optimize intervention outcomes. A subgroup-based approach that integrates, among others, tissue-specific IR, cardiometabolic parameters, anthropometrics, gut microbiota, age, sex, ethnicity, and psychological factors may thereby increase the efficacy of dietary interventions. Nevertheless, the implementation of more personalized nutrition may be complex, costly, and time consuming. Future studies are urgently warranted to obtain insight into a more personalized approach to nutritional interventions, taking into account the metabolic phenotype to ultimately improve insulin sensitivity and reduce the risk for cardiometabolic diseases.

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“…Subjects also received a continuous intravenous infusion of [ 2 H 2 ]-palmitate (97 % enrichment, Cambridge Isotope Laboratories), complexed to human albumin, which commenced 60 min before the blood sampling (0·035 µM/kg body weight per min). In parallel, skeletal muscle biopsies (m. vastus lateralis) were taken before the start of the experiment during fasting and at the end of the postprandial measurement period to determine intramuscular TAG, diacylglycerol (DAG), NEFA and phospholipid content, their degree of saturation as well the fractional synthetic rate (FSR) of TAG, DAG and phospholipid (8)(9)(10)(11)(12) .…”

Section: Dual-stable-isotope Methodologymentioning

confidence: 99%

“…Additionally, in an earlier study we have shown that overweight insulin-resistant men with the metabolic syndrome show an increased forearm muscle VLDL-TAG extraction (9) . Recent studies compared fasting and postprandial skeletal muscle FA handling, firstly, in individuals with varying degree of IR (10) , and, secondly, in pre-diabetic subjects with IFG and/or IGT (11) . In the first study, seventy-four overweight participants (males and females) were divided in two groups based on the homeostasis model assessment for IR median.…”

Section: Skeletal Muscle Lipid Uptakementioning

confidence: 99%

Characterisation of fatty acid metabolism in different insulin-resistant phenotypes by means of stable isotopes

Blaak

2017

Proc. Nutr. Soc.

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The obese insulin resistant and/or prediabetic state is characterised by systemic lipid overflow, mainly driven by an impaired lipid buffering capacity of adipose tissue, and an impaired capacity of skeletal muscle to increase fat oxidation upon increased supply. This leads to the accumulation of bioactive lipid metabolites in skeletal muscle interfering with insulin sensitivity via various mechanisms. In this review, the contribution of dietary v. endogenous fatty acids to lipid overflow, their extraction or uptake by skeletal muscle as well as the fractional synthetic rate, content and composition of the muscle lipid pools is discussed in relation to the development or presence of insulin resistance and/or an impaired glucose metabolism. These parameters are studied in vivo in man by combining a dual stable isotope methodology with [ 2 H 2 ]-and [U-13 C]-palmitate tracers with the arterio-venous balance technique across forearm muscle and biochemical analyses in muscle biopsies. The insulin-resistant state is characterised by an elevated muscle TAG extraction, despite similar supply, and a reduced skeletal muscle lipid turnover, in particular after intake of a high fat, SFA fat meal, but not after a high fat, PUFA meal. Data are placed in the context of current literature, and underlying mechanisms and implications for long-term nutritional interventions are discussed. The prevalence of overweight and overweight-related metabolic disturbances is increasing at an alarming rate. Worldwide more than 50 % of the adults is overweight (>one billion individuals) and a further 12 % (475 million) can be classified as clinically obese. Every year at least 2·8 million adults die as a result of being overweight/obese (http://www.who.int/gho/ncd/risk_fac-tors/overweight/en). Obesity is an important risk factor for chronic metabolic diseases such as type 2 diabetes mellitus (T2DM) and CVD. A disturbed lipid metabolism in multiple tissues, including adipose tissue, liver, skeletal muscle, gut and pancreas may play an important role in the development of insulin resistance (IR), an impaired glucose metabolism and T2DM. These disturbances, in particular an impaired adipose tissue lipid handling, may lead to systemic lipid overflow, increased circulating concentrations of NEFA and TAG and accumulation of lipids in non-adipose tissues (1)(2)(3)(4) . This lipid overflow together with an impaired capacity to adjust fatty acid (FA) oxidation to FA supply in skeletal muscle (metabolic inflexibility (3) ) may cause excess fat storage in skeletal muscle, which is related to the development or worsening of IR. IR in concert with progressive β-cell failure leads to an increased blood glucose concentration in the non-diabetic range, classified as impaired fasting glucose (IFG) or impaired glucose tolerance (IGT). IFG (fasting glucose >5·6 mM/l) and IGT (2 h oral glucose tolerance testderived glucose concentration >7·8 mM) are intermediate states in the transition from a normal glucose tolerance towards T2DM. IFG and IGT may represent dis...

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Altered Skeletal Muscle Fatty Acid Handling in Subjects with Impaired Glucose Tolerance as Compared to Impaired Fasting Glucose

Cited by 22 publications

References 37 publications

Current metabolic perspective on malnutrition in obesity: towards more subgroup-based nutritional approaches?

Current metabolic perspective on malnutrition in obesity: towards more subgroup-based nutritional approaches?

Ectopic Fat Accumulation in Distinct Insulin Resistant Phenotypes; Targets for Personalized Nutritional Interventions

Characterisation of fatty acid metabolism in different insulin-resistant phenotypes by means of stable isotopes

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