ArticleDiabetes2014
Chronic reduction of plasma free fatty acid improves mitochondrial function and whole-body insulin sensitivity in obese and type 2 diabetic individuals.
Article in Diabetes, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers, 1 of them a synthesis that pooled it.
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Who cites it
42 citing papers in PubMed, 1 synthesis or guideline pooled it, 84 citations in OpenAlex.
- Effects of Anthocyanins on Cardiometabolic Health: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.Advances in nutrition (Bethesda, Md.) · 2017Pooled it
- Common variants associated with changes in levels of circulating free fatty acids after administration of glucose-insulin-potassium (GIK) therapy in the IMMEDIATE trial.The pharmacogenomics journal · 2017Trial
- Dapagliflozin Enhances Fat Oxidation and Ketone Production in Patients With Type 2 Diabetes.Diabetes care · 2016 · on this mapTrial
- Metabolic Effects of Long-Term Reduction in Free Fatty Acids With Acipimox in Obesity: A Randomized Trial.The Journal of clinical endocrinology and metabolism · 2016Trial
- Effect of Dapagliflozin With and Without Acipimox on Insulin Sensitivity and Insulin Secretion in T2DM Males.The Journal of clinical endocrinology and metabolism · 2016Trial
- Lipid Signatures Associated with Diabetic Peripheral Neuropathy in Obesity and Type 2 Diabetes-A Systematic Review.Journal of clinical medicine · 2026Review
- Association between free fatty acids and adverse outcomes in patients with and without diabetes undergoing percutaneous coronary intervention.Journal of translational internal medicine · 2026Article
- Effect of acipimox on skeletal muscle biochemistry, structure and function in older people with probable sarcopenia: an experimental medicine study.GeroScience · 2025Article
- The BET inhibitor JQ1 targets fat metabolism and counteracts obesity.Journal of advanced research · 2025Article
- Article
- Nicotinic acid improves mitochondrial function and associated transcriptional pathways in older inactive males.Translational exercise biomedicine · 2024Article
- The impact of forearm immobilization and acipimox administration on muscle amino acid metabolism and insulin sensitivity in healthy, young volunteers.American journal of physiology. Endocrinology and metabolism · 2024Article
- Mitochondrial fatty acid synthesis is an emergent central regulator of mammalian oxidative metabolism.Cell metabolism · 2024Review
- White adipose tissue mitochondrial bioenergetics in metabolic diseases.Reviews in endocrine & metabolic disorders · 2023Review
- The impact of short-term forearm immobilization and acipimox administration on muscle amino acid metabolism and insulin sensitivity in healthy, young volunteers.bioRxiv : the preprint server for biology · 2023Article
- Brain Dopamine-Clock Interactions Regulate Cardiometabolic Physiology: Mechanisms of the Observed Cardioprotective Effects of Circadian-Timed Bromocriptine-QR Therapy in Type 2 Diabetes Subjects.International journal of molecular sciences · 2023Review
- HM-chromanone isolated fromToxicology research · 2023Article
- Heterogeneity in the effect of marked weight loss on metabolic function in women with obesity.JCI insight · 2023Article
- Berberine mitigates hepatic insulin resistance by enhancing mitochondrial architecture via the SIRT1/Opa1 signalling pathway.Acta biochimica et biophysica Sinica · 2022Article
- Effects of Sustained Hyperglycemia on Skeletal Muscle Lipids in Healthy Subjects.The Journal of clinical endocrinology and metabolism · 2022Article
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
Insulin resistance and dysregulation of free fatty acid (FFA) metabolism are core defects in type 2 diabetic (T2DM) and obese normal glucose tolerant (NGT) individuals. Impaired muscle mitochondrial function (reduced ATP synthesis) also has been described in insulin-resistant T2DM and obese subjects. We examined whether reduction in plasma FFA concentration with acipimox improved ATP synthesis rate and altered reactive oxygen species (ROS) production. Eleven NGT obese and 11 T2DM subjects received 1) OGTT, 2) euglycemic insulin clamp with muscle biopsy, and 3) (1)H-magnetic resonance spectroscopy of tibialis anterior muscle before and after acipimox (250 mg every 6 h for 12 days). ATP synthesis rate and ROS generation were measured in mitochondria isolated from muscle tissue ex vivo with chemoluminescence and fluorescence techniques, respectively. Acipimox 1) markedly reduced the fasting plasma FFA concentration and enhanced suppression of plasma FFA during oral glucose tolerance tests and insulin clamp in obese NGT and T2DM subjects and 2) enhanced insulin-mediated muscle glucose disposal and suppression of hepatic glucose production. The improvement in insulin sensitivity was closely correlated with the decrease in plasma FFA in obese NGT (r = 0.81) and T2DM (r = 0.76) subjects (both P < 0.001). Mitochondrial ATP synthesis rate increased by >50% in both obese NGT and T2DM subjects and was strongly correlated with the decrease in plasma FFA and increase in insulin-mediated glucose disposal (both r > 0.70, P < 0.001). Production of ROS did not change after acipimox. Reduction in plasma FFA in obese NGT and T2DM individuals improves mitochondrial ATP synthesis rate, indicating that the mitochondrial defect in insulin-resistant individuals is, at least in part, reversible.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.