Increased mitogen-activated protein kinase expression and activity in white adipose tissue of ventromedial hypothalamus-lesioned rats

Abstract

In rats made obese by electrolytic lesion of the ventromedial hypothalamus (VMH), the onset of the syndrome is determined by the time of the lesion, allowing a chronological study of the alterations associated with obesity. Lesion of the VMH induces hyperphagia, hyperinsulinaemia and obesity [1], associated with alterations in the cellularity and metabolism of the white adipose tissue (WAT). After the lesion, there is an initial period of rapid weight gain (dynamic phase) followed by a slowing in the rate of weight gain (static phase). During the dynamic phase of the VMH obesity, a state of hyperresponsiveness to insulin is observed in white adipose tissue [2]. This Diabetologia (1997) 40: 533-540 Increased mitogen-activated protein kinase expression and activity in white adipose tissue of ventromedial hypothalamus-lesioned rats Summary Ventromedial hypothalamus lesions in rats induce hyperphagia and hyperinsulinaemia associated with a rapid growth of white adipose tissue resulting in massive obesity. It has been shown previously that at an early stage after the lesion, during the dynamic phase of obesity, the white adipose tissue is hyper-responsive to insulin. In the present work, we show that the effects of insulin on the autophosphorylation of the insulin receptor and on its tyrosine-kinase activity towards endogenous substrates are similar in intact adipocytes of control and ventromedial hypothalamus lesioned rats. One week after the lesion, the expression of phosphatidylinisitol 3-kinase and RAF-1 kinase, evaluated by Western-blotting, was similar in control and ventromedial hypothalamus lesioned rats. In contrast, an important increase in the expression of extracellular signal regulated kinase 1 protein was observed in white adipose tissue of ventromedial hypothalamus lesioned compared to control animals. No difference in the expression of extracellular signal regulated kinase 1 mRNA was observed in adipose tissue of control and ventromedial hypothalamus lesioned rats, suggesting that a posttranscriptional mechanism is involved in the over-expression of extracellular signal regulated kinase 1. The kinase activity of extracellular signal regulated kinase 1 and 2 is also markedly increased in adipocytes of ventromedial hypothalamus lesioned compared to control rats, both in the basal state and after insulin stimulation. Six weeks after the ventromedial hypothalamus lesion, this increase in mitogen-activated protein kinase expression and activity was still observed in adipocytes of ventromedial hypothalamus lesioned rats. These results suggest that an early and sustained increase in the expression and activity of mitogen-activated protein kinase may participate in the development of white adipose tissue in ventromedial hypothalamus lesioned rats. [Diabetologia (1997) 40: 533-540]

Gene expression in normal-weight mice offspring from parents on Western Diets suggests altered risk for obesity and metabolic disease

“…LRRK2 has been shown to affect signal transduction pathways, including the ERK module, and may in uence autophagy (Carballo-Carbajal et al 2010). Interestingly, the ERK pathway is known to be upregulated in adipose tissue in response to certain stimuli, including diet-induced obesity (Combettes-Souverain et al 1997). Lastly, Feng et al (2011) investigated whether adipocyte cell death is a consequence of macrophage in ammation, or vice versa, in the context of a high-fat diet, and suggested that a adipocyte cell death is an intrinsic response independent of macrophage in ltration, which may explain the upregulation of PDCD10 in INGWAT.…”

Rat uncoupling protein 2 (UCP2): Expression in obese ventromedial hypothalamus (VMH)-lesioned animals

“…Rats were anaesthetized intraperitoneally with 95 mg ketamineakg body weight (Imalgene 500, Bio-Me Ârieux, France) and VMH lesions were carried out as described previously. 14,15 For the determination of blood glucose, plasma insulin and plasma lipids, a catheter was implanted into the carotid artery as previously described.…”