scholarly journals Fatty Acid Incubation of Myotubes From Humans With Type 2 Diabetes Leads to Enhanced Release of  -Oxidation Products Because of Impaired Fatty Acid Oxidation: Effects of Tetradecylthioacetic Acid and Eicosapentaenoic Acid

Diabetes ◽  
2008 ◽  
Vol 58 (3) ◽  
pp. 527-535 ◽  
Author(s):  
A. J. Wensaas ◽  
A. C. Rustan ◽  
M. Just ◽  
R. K. Berge ◽  
C. A. Drevon ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Fatty Acid ◽  
Eicosapentaenoic Acid ◽  
Fatty Acid Oxidation ◽  
Oxidation Products ◽  
Acid Oxidation ◽  
Tetradecylthioacetic Acid ◽  
Impaired Fatty Acid

scholarly journals Assessment of myocardial metabolic flexibility and work efficiency in human type 2 diabetes using 16-[18F]fluoro-4-thiapalmitate, a novel PET fatty acid tracer

2016 ◽  
Vol 310 (6) ◽  
pp. E452-E460 ◽  
Author(s):  
K. J. Mather ◽  
G. D. Hutchins ◽  
K. Perry ◽  
W. Territo ◽  
R. Chisholm ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Oxygen Consumption ◽  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Acid Oxidation ◽  
Metabolic Flexibility ◽  
Work Efficiency ◽  
Myocardial Fatty Acid ◽  
Fuel Selection

Altered myocardial fuel selection likely underlies cardiac disease risk in diabetes, affecting oxygen demand and myocardial metabolic flexibility. We investigated myocardial fuel selection and metabolic flexibility in human type 2 diabetes mellitus (T2DM), using positron emission tomography to measure rates of myocardial fatty acid oxidation {16-[18F]fluoro-4-thia-palmitate (FTP)} and myocardial perfusion and total oxidation ([11C]acetate). Participants underwent paired studies under fasting conditions, comparing 3-h insulin + glucose euglycemic clamp conditions (120 mU·m−2·min−1) to 3-h saline infusion. Lean controls ( n = 10) were compared with glycemically controlled volunteers with T2DM ( n = 8). Insulin augmented heart rate, blood pressure, and stroke index in both groups (all P < 0.01) and significantly increased myocardial oxygen consumption ( P = 0.04) and perfusion ( P = 0.01) in both groups. Insulin suppressed available nonesterified fatty acids ( P < 0.0001), but fatty acid concentrations were higher in T2DM under both conditions ( P < 0.001). Insulin-induced suppression of fatty acid oxidation was seen in both groups ( P < 0.0001). However, fatty acid oxidation rates were higher under both conditions in T2DM ( P = 0.003). Myocardial work efficiency was lower in T2DM ( P = 0.006) and decreased in both groups with the insulin-induced increase in work and shift in fuel utilization ( P = 0.01). Augmented fatty acid oxidation is present under baseline and insulin-treated conditions in T2DM, with impaired insulin-induced shifts away from fatty acid oxidation. This is accompanied by reduced work efficiency, possibly due to greater oxygen consumption with fatty acid metabolism. These observations suggest that improved fatty acid suppression, or reductions in myocardial fatty acid uptake and retention, could be therapeutic targets to improve myocardial ischemia tolerance in T2DM.

scholarly journals Blunted Reduction of Postprandial Acylcarnitine in Type 2 Diabetes and Identification of C16:0 as a New Marker of Excessive Fatty Acid Oxidation

2013 ◽  
Vol 37 ◽  
pp. S62
Author(s):  
Fatima-Zahra Bouchouirab ◽  
Mélanie Fortin ◽  
Frédérique Frish ◽  
Jean Dubé ◽  
André Carpentier
Keyword(s):  
Type 2 Diabetes ◽  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Acid Oxidation

Lipid metabolism, exercise and insulin action

2006 ◽  
Vol 42 ◽  
pp. 47-59 ◽  
Author(s):  
Arend Bonen ◽  
G. Lynis Dohm ◽  
Luc J.C. van Loon
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Insulin Signalling ◽  
Acid Oxidation ◽  
Fatty Acid Transport ◽  
Acid Transport ◽  
Severely Obese

Skeletal muscle constitutes 40% of body mass and takes up 80% of a glucose load. Therefore, impaired glucose removal from the circulation, such as that which occurs in obesity and type 2 diabetes, is attributable in large part to the insulin resistance in muscle. Recent research has shown that fatty acids, derived from adipose tissue, can interfere with insulin signalling in muscle. Hence, insulin-stimulated GLUT4 translocation to the cell surface is impaired, and therefore, the rate of glucose removal from the circulation into muscle is delayed. The mechanisms provoking lipid-mediated insulin resistance are not completely understood. In sedentary individuals, excess intramyocellular accumulation of triacylglycerols is only modestly associated with insulin resistance. In contrast, endurance athletes, despite accumulating large amounts of intramyocellular triacylglycerols, are highly insulin sensitive. Thus it appears that lipid metabolites, other than triacylglycerols, interfere with insulin signalling. These metabolites, however, are not expected to accumulate in athletic muscles, as endurance training increases the capacity for fatty acid oxidation by muscle. These observations, and others in severely obese individuals and type 2 diabetes patients, suggest that impaired rates of fatty acid oxidation are associated with insulin resistance. In addition, in obesity and type 2 diabetes, the rates of fatty acid transport into muscle are also increased. Thus, excess intracellular lipid metabolite accumulation, which interferes with insulin signalling, can occur as a result of impaired rates of fatty acid oxidation and/or increased rates of fatty acid transport into muscle. Accumulation of excess intramyocellular lipid can be avoided by exercise, which improves the capacity for fatty acid oxidation.

scholarly journals Susceptibility of podocytes to palmitic acid is regulated by fatty acid oxidation and inversely depends on acetyl-CoA carboxylases 1 and 2

2014 ◽  
Vol 306 (4) ◽  
pp. F401-F409 ◽  
Author(s):  
Kapil Kampe ◽  
Jonas Sieber ◽  
Jana Marina Orellana ◽  
Peter Mundel ◽  
Andreas Werner Jehle
Keyword(s):  
Type 2 Diabetes ◽  
Fatty Acid ◽  
Palmitic Acid ◽  
Er Stress ◽  
Fatty Acid Oxidation ◽  
Acid Oxidation ◽  
Genome Wide Association Studies ◽  
Acetyl Coa ◽  
Stimulation Of

Type 2 diabetes is characterized by dyslipidemia with elevated free fatty acids (FFAs). Loss of podocytes is a hallmark of diabetic nephropathy, and podocytes are susceptible to saturated FFAs, which induce endoplasmic reticulum (ER) stress and podocyte death. Genome-wide association studies indicate that expression of acetyl-CoA carboxylase (ACC) 2, a key enzyme of fatty acid oxidation (FAO), is associated with proteinuria in type 2 diabetes. Here, we show that stimulation of FAO by aminoimidazole-4-carboxamide-1β-d-ribofuranoside (AICAR) or by adiponectin, activators of the low-energy sensor AMP-activated protein kinase (AMPK), protects from palmitic acid-induced podocyte death. Conversely, inhibition of carnitine palmitoyltransferase (CPT-1), the rate-limiting enzyme of FAO and downstream target of AMPK, augments palmitic acid toxicity and impedes the protective AICAR effect. Etomoxir blocked the AICAR-induced FAO measured with tritium-labeled palmitic acid. The beneficial effect of AICAR was associated with a reduction of ER stress, and it was markedly reduced in ACC-1/-2 double-silenced podocytes. In conclusion, the stimulation of FAO by modulating the AMPK-ACC-CPT-1 pathway may be part of a protective mechanism against saturated FFAs that drive podocyte death. Further studies are needed to investigate the potentially novel therapeutic implications of these findings.

scholarly journals Resistin Regulates Fatty Acid Β Oxidation by Suppressing Expression of Peroxisome Proliferator Activator Receptor Gamma-Coactivator 1α (PGC-1α)

2018 ◽  
Vol 46 (5) ◽  
pp. 2165-2172 ◽  
Author(s):  
Fang He ◽  
Jie-Qiong Jin ◽  
Qing-Qing Qin ◽  
Yong-Qin Zheng ◽  
Ting-Ting Li ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Regulatory Genes ◽  
Acid Oxidation ◽  
Fatty Acid Transport ◽  
Acid Transport ◽  
Inhibitory Effects ◽  
Transcriptional Regulatory

Background/Aims: Abnormal fatty acid β oxidation has been associated with obesity and type 2 diabetes. Resistin is an adipokine that has been considered as a potential factor in obesity-mediated insulin resistance and type 2 diabetes. However, the effect of resistin on fatty acid β oxidation needs to be elucidated. Methods: We detected the effects of resistin on the expression of fatty acid oxidation (FAO) transcriptional regulatory genes, the fatty acid transport gene, and mitochondrial β-oxidation genes using real-time PCR. The rate of FAO was measured using 14C-palmitate. Immunofluorescence assay and western blot analysis were used to explore the underlying molecular mechanisms. Results: Resistin leads to a reduction in expression of the FAO transcriptional regulatory genes ERRα and NOR1, the fatty acid transport gene CD36, and the mitochondrial β-oxidation genes CPT1, MCAD, and ACO. Importantly, treatment with resistin led to a reduction in the rate of cellular fatty acid oxidation. In addition, treatment with resistin reduced phosphorylation of acetyl CoA carboxylase (ACC) (inhibitory). Mechanistically, resistin inhibited the activation of CREB, resulting in suppression of PGC-1α. Importantly, overexpressing PGC-1α can rescue the inhibitory effects of resistin on fatty acid β oxidation. Conclusions: Activating the transcriptional activity of CREB using small molecular chemicals is a potential pharmacological strategy for preventing the inhibitory effects of resistin on fatty acid β oxidation.

scholarly journals Muscle-Specific Overexpression of CD36 Reverses the Insulin Resistance and Diabetes of MKR Mice

Endocrinology ◽  
2004 ◽  
Vol 145 (10) ◽  
pp. 4667-4676 ◽  
Author(s):  
Lisa Héron-Milhavet ◽  
Martin Haluzik ◽  
Shoshana Yakar ◽  
Oksana Gavrilova ◽  
Stephanie Pack ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Cell Function ◽  
Dominant Negative ◽  
Whole Body ◽  
Acid Oxidation

Abstract Insulin resistance is one of the primary characteristics of type 2 diabetes. Mice overexpressing a dominant-negative IGF-I receptor specifically in muscle (MKR mice) demonstrate severe insulin resistance with high levels of serum and tissue lipids and eventually develop type 2 diabetes at 5–6 wk of age. To determine whether lipotoxicity plays a role in the progression of the disease, we crossed MKR mice with mice overexpressing a fatty acid translocase, CD36, in skeletal muscle. The double-transgenic MKR/CD36 mice showed normalization of the hyperglycemia and the hyperinsulinemia as well as a marked improvement in liver insulin sensitivity. The MKR/CD36 mice also exhibited normal rates of fatty acid oxidation in skeletal muscle when compared with the decreased rate of fatty acid oxidation in MKR. With the reduction in insulin resistance, β-cell function returned to normal. These and other results suggest that the insulin resistance in the MKR mice is associated with increased muscle triglycerides levels and that whole-body insulin resistance can be, at least partially, reversed in association with a reduction in muscle triglycerides levels, although the mechanisms are yet to be determined.

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