Tissue-Specific Inactivation of Type 2 Deiodinase Reveals Multilevel Control of Fatty Acid Oxidation by Thyroid Hormone in the Mouse. Diabetes 2014;63:1594-1604

The antiobesity and antidiabetic effects of the β3-adrenergic agonists were investigated on nonobese type 2 diabetic MKR mice after injection with a β3-adrenergic agonist, CL-316243. An intact response to acute CL-316243 treatment was observed in MKR mice. Chronic intraperitoneal CL-316243 treatment of MKR mice reduced blood glucose and serum insulin levels. Hyperinsulinemic euglycemic clamps exhibited improvement of the whole body insulin sensitivity and glucose homeostasis concurrently with enhanced insulin action in liver and adipose tissue. Treating MKR mice with CL-316243 significantly lowered serum and hepatic lipid levels, in part due to increased whole body triglyceride clearance and fatty acid oxidation in adipocytes. A significant reduction in total body fat content and epididymal fat weight was observed along with enhanced metabolic rate in both wild-type and MKR mice after treatment. These data demonstrate that β3-adrenergic activation improves the diabetic state of nonobese diabetic MKR mice by potentiation of free fatty acid oxidation by adipose tissue, suggesting a potential therapeutic role for β3-adrenergic agonists in nonobese diabetic subjects.

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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 ◽

10.2337/db08-1043 ◽

2008 ◽

Vol 58 (3) ◽

pp. 527-535 ◽

Cited By ~ 47

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

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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

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00437.2015 ◽

2016 ◽

Vol 310 (6) ◽

pp. E452-E460 ◽

Cited By ~ 25

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.

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Weight Reduction and the Impaired Plasma-Derived Free Fatty Acid Oxidation in Type 2 Diabetic Subjects1

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jcem.86.4.7397 ◽

2001 ◽

Vol 86 (4) ◽

pp. 1638-1644

Author(s):

E. E. Blaak ◽

B. H. R. Wolffenbuttel ◽

W. H. M. Saris ◽

M. M. A. L. Pelsers ◽

A. J. M. Wagenmakers

Keyword(s):

Fatty Acid ◽

Free Fatty Acid ◽

Fatty Acid Oxidation ◽

Weight Reduction ◽

Acid Oxidation ◽

Free Fatty Acid Oxidation ◽

Type 2 Diabetic

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

Canadian Journal of Diabetes ◽

10.1016/j.jcjd.2013.08.188 ◽

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

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Effects of blockade of fatty acid oxidation on whole body and tissue-specific glucose metabolism in rats

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1993.265.4.e592 ◽

1993 ◽

Vol 265 (4) ◽

pp. E592-E600 ◽

Cited By ~ 4

Author(s):

A. B. Jenkins ◽

L. H. Storlien ◽

G. J. Cooney ◽

G. S. Denyer ◽

I. D. Caterson ◽

...

Keyword(s):

Skeletal Muscle ◽

Fatty Acid ◽

Glucose Metabolism ◽

Fatty Acid Oxidation ◽

Pyruvate Dehydrogenase ◽

Glucose Utilization ◽

Whole Body ◽

Acid Oxidation ◽

Tissue Specific ◽

Glucose Output

We examined the effect of the long-chain fatty acid oxidation blocker methyl palmoxirate (methyl 2-tetradecyloxiranecarboxylate, McN-3716) on glucose metabolism in conscious rats. Fasted animals [5 h with or without hyperinsulinemia (100 mU/l) and 24 h] received methyl palmoxirate (30 or 100 mg/kg body wt po) or vehicle 30 min before a euglycemic glucose clamp. Whole body and tissue-specific glucose metabolism were calculated from 2-deoxy-[3H]-glucose kinetics and accumulation. Oxidative metabolism was assessed by respiratory gas exchange in 24-h fasted animals. Pyruvate dehydrogenase complex activation was determined in selected tissues. Methyl palmoxirate suppressed whole body lipid oxidation by 40-50% in 24-h fasted animals, whereas carbohydrate oxidation was stimulated 8- to 10-fold. Whole body glucose utilization was not significantly affected by methyl palmoxirate under any conditions; hepatic glucose output was suppressed only in the predominantly gluconeogenic 24-h fasted animals. Methyl palmoxirate stimulated glucose uptake in heart in 24-h fasted animals [15 +/- 5 vs. 220 +/- 28 (SE) mumol x 100 g-1 x min-1], with smaller effects in 5-h fasted animals with or without hyperinsulinemia. Methyl palmoxirate induced significant activation of pyruvate dehydrogenase in heart in the basal state, but not during hyperinsulinemia. In skeletal muscles, methyl palmoxirate suppressed glucose utilization in the basal state but had no effect during hyperinsulinemia; pyruvate dehydrogenase activation in skeletal muscle was not affected by methyl palmoxirate under any conditions. The responses in skeletal muscle are consistent with the operation of a mechanism similar to the Pasteur effect.(ABSTRACT TRUNCATED AT 250 WORDS)

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