Palmitic acid mediates hypothalamic insulin resistance by altering PKC-θ subcellular localization in rodents

Abstract

During the preparation of the manuscript, the number of samples used for the quantification of RT-PCR depicted in Figure 2E was stated incorrectly. The corrected legend appears below.(E) mRNA expression of TRPA1 and TRPM8 in the DRG after inflammation, as detected by RT-PCR. Quantification of RT-PCR data is shown at right. Data represent mean ± SD; n = 3 per group. *P < 0.05 compared with the naive control.The authors regret the error. During the preparation of the manuscript, the vehicle for ICV fatty acid infusion was incorrectly described. The incorrect description is on page 2586. The corrected paragraph appears below. Fatty acid infusion.Oleate (Oleic Acid-Cyclodextrin Complex; Sigma-Aldrich) was dissolved in PBS. Palmitate was first dissolved in absolute ethanol to make a 5 mM stock solution, which was then further dissolved in PBS. Rats were implanted with a cannula aimed into the third ventricle as described above. The cannula was connected via a polyethylene catheter to a subcutaneous osmotic minipump (Alza Corporation) filled with either palmitic or oleic acid (equimolar concentrations, 10 μmol/l) or vehicle (PBS) for continuous infusion over 3 days. The fatty acids were infused at a rate of 12 μl/d (or 8.3 nl/min); thus, we infused a total volume of 36 μl/3 d, which represents 1.8 nmol/3 d (i.e., 0.41 pmol/min).The authors regret the error.

High cerebral insulin sensitivity is associated with loss of body fat during lifestyle intervention

“…At that time, we speculated that fatty acids derived from visceral fat depots may cause insulin resistance of the brain and therefore lead to further weight gain. Indeed, recent studies confirmed that intracerebroventricular palmitic acid infusion and high-fat diet induce insulin resistance in different brain regions in mice and rats [12,14,15]. These observations, together with the present finding of high insulin sensitivity in the brain associated with lower intake of saturated fat, may suggest that insulin resistance in the brain elevates serum concentrations of saturated fatty acids not only by increasing visceral fat mass, but also more directly by decreasing physical activity and increasing intake of saturated fat.…”

Protein Kinase C-Theta Is Required for Development of Experimental Cerebral Malaria

“…It is also expressed in natural killer cells 39 ; in platelets, where it may modulate activation and thrombus formation 40 ; in skeletal muscle cells 41 ; in the endothelium of muscle resistance arteries, where it modulates vascular tone through insulin-induced vasoconstriction 42 ; and in hypothalamus tissue, where it contributes to insulin signaling. 43 PKC-could, therefore, exert multifold influence on development of CM, through platelet activation and vascular tone modulation, beyond a direct effect on T cells.…”

Rôle de la détection centrale des lipides dans le contrôle nerveux de la balance énergétique

“…L'administration intrahypothalamique de C75, un inhibiteur de FAS, qui induit également une augmentation de la concentration en acyl-CoA, diminue la prise alimentaire et induit une baisse du poids corporel [28]. [36]. Lorsqu'on perfuse in vivo du palmitate par voie intracérébroventriculaire chez le rat, on provoque un ancrage de la PKC  dans la membrane plasmique, ce qui a pour conséquence de l'activer et, consécutivement, de perturber la voie de signalisation hypothalamique de l'insuline [36].…”

“…[36]. Lorsqu'on perfuse in vivo du palmitate par voie intracérébroventriculaire chez le rat, on provoque un ancrage de la PKC  dans la membrane plasmique, ce qui a pour conséquence de l'activer et, consécutivement, de perturber la voie de signalisation hypothalamique de l'insuline [36]. On induit ainsi une résistance hypothalamique et, en conséquence, l'apparition d'une résistance à l'insuline hépatique, démontrant que l'apport excessif de lipides au niveau central perturbe le contrôle nerveux de la production hépatique de glucose, rendant l'insuline moins efficace.…”

“…On induit ainsi une résistance hypothalamique et, en conséquence, l'apparition d'une résistance à l'insuline hépatique, démontrant que l'apport excessif de lipides au niveau central perturbe le contrôle nerveux de la production hépatique de glucose, rendant l'insuline moins efficace. L'effet délétère du palmitate peut-être atténué lorsqu'on diminue l'expression de la PKC  par une approche génétique spécifiquement dans le noyau arqué [36]. Enfin, un travail tout à fait intéressant montre que les acides gras pourraient également jouer un rôle dans la plasticité neuronale hypothalamique comme décrit par Benani et al [37].…”