Leptin stimulates fatty-acid oxidation by activating AMP-activated protein kinase

@article{Minokoshi2002LeptinSF,
  title={Leptin stimulates fatty-acid oxidation by activating AMP-activated protein kinase},
  author={Yasuhiko Minokoshi and Young-Bum Kim and Odile D. Peroni and Lee G. D. Fryer and C. M{\"u}ller and David Carling and Barbara B. Kahn},
  journal={Nature},
  year={2002},
  volume={415},
  pages={339-343}
}
Leptin is a hormone secreted by adipocytes that plays a pivotal role in regulating food intake, energy expenditure and neuroendocrine function. Leptin stimulates the oxidation of fatty acids and the uptake of glucose, and prevents the accumulation of lipids in nonadipose tissues, which can lead to functional impairments known as “lipotoxicity”. The signalling pathways that mediate the metabolic effects of leptin remain undefined. The 5′-AMP-activated protein kinase (AMPK) potently stimulates… 
Adiponectin stimulates glucose utilization and fatty-acid oxidation by activating AMP-activated protein kinase
TLDR
It is shown that phosphorylation and activation of the 5′-AMP-activated protein kinase (AMPK) are stimulated with globular and full-length Ad in skeletal muscle and only with full- lengths Ad in the liver, indicating that stimulation of glucose utilization and fatty-acid oxidation by Ad occurs through activation of AMPK.
Functions of AMP‐activated protein kinase in adipose tissue
TLDR
Since fatty acids have a key role in insulin resistance, especially in muscles, activating AMPK in adipose tissue might be found to be beneficial in insulin‐resistant states, particularly as AMPK activation also reduces cytokine secretion in adipocytes.
The suppressor of cytokine signaling 3 inhibits leptin activation of AMP-kinase in cultured skeletal muscle of obese humans.
TLDR
The data suggest that this impairment of leptin signaling in skeletal muscle may contribute to the aberrant regulation of fatty acid metabolism observed in obesity and that pharmacological activation of AMPK may be an effective therapy to bypass SOCS3-mediated skeletal muscle leptin resistance for the treatment of obesity-related disorders.
Role of AMP-activated protein kinase in adipose tissue metabolism and inflammation.
TLDR
The role of AMPK in adipose tissue is discussed, focussing on the regulation of carbohydrate and lipid metabolism, adipogenesis and pro-inflammatory pathways in physiological and pathophysiological conditions.
AMP-activated Protein Kinase Plays a Role in the Control of Food Intake*
TLDR
It is demonstrated that counter-regulatory hormones involved in appetite control regulate AMPK activity and that pharmacological activation of AMPK in the hypothalamus increases food intake, and that AMPK is identified as a novel target for anti-obesity drugs.
AMP‐activated protein kinase: role in metabolism and therapeutic implications
TLDR
Evidence that pharmacological activation of AMPK in vivo improves blood glucose homeostasis, cholesterol concentrations and blood pressure in insulin‐resistant rodents, make this enzyme an attractive pharmacological target for the treatment of type 2 diabetes, ischaemic heart disease and other metabolic diseases.
AMP-activated protein kinase in the heart: role in cardiac glucose and fatty acid metabolism
TLDR
This review focuses on the emerging information regarding the regulation of AMPK, its role in cardiac glucose and fatty acid metabolism and its influence on cell death.
Chronic Hexosamine Flux Stimulates Fatty Acid Oxidation by Activating AMP-activated Protein Kinase in Adipocytes*
TLDR
Chronic high hexosamine flux stimulates fatty acid oxidation by activating AMPK in adipocytes, in part through O-linked glycosylation, demonstrating that AMPK is regulated by the HBP.
Leptin Activates Hepatic 5′-AMP-activated Protein Kinase through Sympathetic Nervous System and α1-Adrenergic Receptor
TLDR
It is demonstrated that leptin activates hepatic AMPK through the central nervous system and α-adrenergic sympathetic nerves, which indicates that the down-regulation of hepaticAMPK activities plays a pathophysiological role in the metabolic disturbances of lipodystrophy.
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 39 REFERENCES
AMP-activated protein kinase, a metabolic master switch: possible roles in Type 2 diabetes.
  • W. Winder, D. Hardie
  • Biology, Medicine
    American journal of physiology. Endocrinology and metabolism
  • 1999
TLDR
Increased recruitment of the AMPK signaling system, either by exercise or pharmaceutical activators, may be effective in correcting insulin resistance in patients with forms of impaired glucose tolerance and Type 2 diabetes resulting from defects in the insulin signaling cascade.
Activation of glucose transport by AMP-activated protein kinase via stimulation of nitric oxide synthase.
TLDR
Results indicate that activation of AMPK in muscle cells stimulates glucose transport by activation of NOS coupled to downstream signaling components, including cyclic GMP.
Dual regulation of the AMP‐activated protein kinase provides a novel mechanism for the control of creatine kinase in skeletal muscle
TLDR
The novel regulation of AMPK described here provides a mechanism by which energy supply can meet energy demand following the utilization of the immediate energy reserve provided by the creatine kinase–phosphocreatine system.
Metabolic stress and altered glucose transport: activation of AMP-activated protein kinase as a unifying coupling mechanism.
TLDR
The activation of AMPK may be a common mechanism leading to insulin-independent glucose transport in skeletal muscle under conditions of metabolic stress, and this hypothesis is tested under several conditions that evoke metabolic stress accompanied by intracellular fuel depletion.
AMP-Activated Protein Kinase Is Activated by the Stimulations of Gq-Coupled Receptors
TLDR
Direct activation of AMPKα1 with treatment of 5-aminoimidazole-4-carboxamide-1-β- d -ribofuranoside did not trigger GLUT4 translocation nor stimulate glucose uptake in cells, thus, activation ofAMPK α1 via Gq is not sufficient to trigger GLut4 translocations or stimulate sugars uptake.
Acute stimulation of glucose metabolism in mice by leptin treatment
TLDR
It is shown that leptin also acts acutely to increase glucose metabolism, although studies of leptin's effect on glucose metabolism have typically been confounded by the weight-reducing actions of leptin treatment, which by itself could affect glucose homoeostasis.
Characterization of the Role of AMP-Activated Protein Kinase in the Regulation of Glucose-Activated Gene Expression Using Constitutively Active and Dominant Negative Forms of the Kinase
TLDR
The results suggest that AMPK is involved in the inhibition of glucose-activated gene expression but not in the induction pathway, and demonstrates that the two mutants generated will provide valuable tools for studying the wider physiological role of AMPK.
Leptin Directly Alters Lipid Partitioning in Skeletal Muscle
TLDR
It is demonstrated that leptin has direct and acute effects on skeletal muscle, and that when both hormones were present, leptin attenuated both the antioxidative and the lipogenic effects of insulin by 50%.
Malonyl-CoA, fuel sensing, and insulin resistance.
TLDR
The hypothesis is that by altering the cytosolic concentrations of LCFA-CoA and diacylglycerol, and secondarily the activity of one or more protein kinase C isoforms, changes in malonyl- coA provide a link between fuel metabolism and signal transduction in these cells.
The regulation of AMP-activated protein kinase by phosphorylation.
TLDR
It is shown that AMPKK phosphorylates at least two other sites on the alpha subunit and one site on the beta subunit, and evidence that phosphorylation of Thr(172) may be involved in the sensitivity of the AMPK complex to AMP is provided.
...
1
2
3
4
...