Limits...
IL-6 and IL-10 anti-inflammatory activity links exercise to hypothalamic insulin and leptin sensitivity through IKKbeta and ER stress inhibition.

Ropelle ER, Flores MB, Cintra DE, Rocha GZ, Pauli JR, Morari J, de Souza CT, Moraes JC, Prada PO, Guadagnini D, Marin RM, Oliveira AG, Augusto TM, Carvalho HF, Velloso LA, Saad MJ, Carvalheira JB - PLoS Biol. (2010)

Bottom Line: Overnutrition caused by overeating is associated with insulin and leptin resistance through IKKbeta activation and endoplasmic reticulum (ER) stress in the hypothalamus.This molecular mechanism, mediated by physical activity, involves the anti-inflammatory protein IL-10, a core inhibitor of IKKbeta/NF-kappaB signaling and ER stress.Hence, inflammatory signaling in the hypothalamus links beneficial physiological effects of exercise to the central action of insulin and leptin.

View Article: PubMed Central - PubMed

Affiliation: Department of Internal Medicine, Faculty of Medical Sciences, State University of Campinas (UNICAMP), Campinas, São Paulo, Brazil.

ABSTRACT
Overnutrition caused by overeating is associated with insulin and leptin resistance through IKKbeta activation and endoplasmic reticulum (ER) stress in the hypothalamus. Here we show that physical exercise suppresses hyperphagia and associated hypothalamic IKKbeta/NF-kappaB activation by a mechanism dependent upon the pro-inflammatory cytokine interleukin (IL)-6. The disruption of hypothalamic-specific IL-6 action blocked the beneficial effects of exercise on the re-balance of food intake and insulin and leptin resistance. This molecular mechanism, mediated by physical activity, involves the anti-inflammatory protein IL-10, a core inhibitor of IKKbeta/NF-kappaB signaling and ER stress. We report that exercise and recombinant IL-6 requires IL-10 expression to suppress hyperphagia-related obesity. Moreover, in contrast to control mice, exercise failed to reverse the pharmacological activation of IKKbeta and ER stress in C3H/HeJ mice deficient in hypothalamic IL-6 and IL-10 signaling. Hence, inflammatory signaling in the hypothalamus links beneficial physiological effects of exercise to the central action of insulin and leptin.

Show MeSH

Related in: MedlinePlus

Exercise induces appetite-suppressive actions in different models of obesity.(A) 12 h of food intake (kcal) in lean and diet-induced obesity (DIO) Wistar rats under resting conditions or after swimming exercise (SW Exe) or treadmill running (TR Exe) (n = 20–35 animals per group). Rats were fasted during 9 h and the hypothalamic levels (B) NPY and (C) POMC mRNA were examined using real time PCR assay. (D) Body weight, (E) epididymal fat pad weight, (F) 12-h food intake of leptin-deficient mice (Leptob/ob) and respective wild type group. (G) NPY and (H) POMC mRNA were examined using real time PCR assay. (I) Body weight and (J) epididymal fat pad weight of wild type and leptin-deficient mice under resting conditions or immediately after the exercise protocols (n = 10 animals per group). Data are the means ± SEM. # p<0.05 versus respective lean group at rest; * p<0.05 versus respective obese group at rest. Lean animals (white bars) and obese animals (black bars).
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2927536&req=5

pbio-1000465-g001: Exercise induces appetite-suppressive actions in different models of obesity.(A) 12 h of food intake (kcal) in lean and diet-induced obesity (DIO) Wistar rats under resting conditions or after swimming exercise (SW Exe) or treadmill running (TR Exe) (n = 20–35 animals per group). Rats were fasted during 9 h and the hypothalamic levels (B) NPY and (C) POMC mRNA were examined using real time PCR assay. (D) Body weight, (E) epididymal fat pad weight, (F) 12-h food intake of leptin-deficient mice (Leptob/ob) and respective wild type group. (G) NPY and (H) POMC mRNA were examined using real time PCR assay. (I) Body weight and (J) epididymal fat pad weight of wild type and leptin-deficient mice under resting conditions or immediately after the exercise protocols (n = 10 animals per group). Data are the means ± SEM. # p<0.05 versus respective lean group at rest; * p<0.05 versus respective obese group at rest. Lean animals (white bars) and obese animals (black bars).

Mentions: It has been demonstrated that physical activity may contribute to the energy balance by increasing energy expenditure. Although the energy expenditure aspects of such exercise may contribute to the effects of weight loss, the effect of exercise on the control of energy intake remains unclear. To evaluate the impact of physical activity on food consumption, we measured the 12-h total energy intake in lean and diet-induced obese (DIO) rats after one bout of swimming (SW Exe) and treadmill running (TR Exe) exercise. Neither of the exercise protocols changed the energy intake in lean animals; however, exercise suppressed the hyperphagic response, mediated by chronic overnutrition, restoring the energy intake to the levels of lean animals (Figure 1A). To assess whether the effects of exercise on food intake are dependent on the neuropeptides modulation, we performed a real time PCR assay to determine the mRNA levels of Neuropeptide-Y (NPY) and Proopiomelanocortin (POMC). After 9 h of fasting, we found that chronic overnutrition increased NPY mRNA and reduced POMC mRNA levels, while physical activity restored the NPY (Figure 1B) and POMC mRNA levels (Figure 1C) in obese animals; on the other hand, exercise did not change the NPY and POMC mRNA levels in lean rats (Figure 1B and C).


IL-6 and IL-10 anti-inflammatory activity links exercise to hypothalamic insulin and leptin sensitivity through IKKbeta and ER stress inhibition.

Ropelle ER, Flores MB, Cintra DE, Rocha GZ, Pauli JR, Morari J, de Souza CT, Moraes JC, Prada PO, Guadagnini D, Marin RM, Oliveira AG, Augusto TM, Carvalho HF, Velloso LA, Saad MJ, Carvalheira JB - PLoS Biol. (2010)

Exercise induces appetite-suppressive actions in different models of obesity.(A) 12 h of food intake (kcal) in lean and diet-induced obesity (DIO) Wistar rats under resting conditions or after swimming exercise (SW Exe) or treadmill running (TR Exe) (n = 20–35 animals per group). Rats were fasted during 9 h and the hypothalamic levels (B) NPY and (C) POMC mRNA were examined using real time PCR assay. (D) Body weight, (E) epididymal fat pad weight, (F) 12-h food intake of leptin-deficient mice (Leptob/ob) and respective wild type group. (G) NPY and (H) POMC mRNA were examined using real time PCR assay. (I) Body weight and (J) epididymal fat pad weight of wild type and leptin-deficient mice under resting conditions or immediately after the exercise protocols (n = 10 animals per group). Data are the means ± SEM. # p<0.05 versus respective lean group at rest; * p<0.05 versus respective obese group at rest. Lean animals (white bars) and obese animals (black bars).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2927536&req=5

pbio-1000465-g001: Exercise induces appetite-suppressive actions in different models of obesity.(A) 12 h of food intake (kcal) in lean and diet-induced obesity (DIO) Wistar rats under resting conditions or after swimming exercise (SW Exe) or treadmill running (TR Exe) (n = 20–35 animals per group). Rats were fasted during 9 h and the hypothalamic levels (B) NPY and (C) POMC mRNA were examined using real time PCR assay. (D) Body weight, (E) epididymal fat pad weight, (F) 12-h food intake of leptin-deficient mice (Leptob/ob) and respective wild type group. (G) NPY and (H) POMC mRNA were examined using real time PCR assay. (I) Body weight and (J) epididymal fat pad weight of wild type and leptin-deficient mice under resting conditions or immediately after the exercise protocols (n = 10 animals per group). Data are the means ± SEM. # p<0.05 versus respective lean group at rest; * p<0.05 versus respective obese group at rest. Lean animals (white bars) and obese animals (black bars).
Mentions: It has been demonstrated that physical activity may contribute to the energy balance by increasing energy expenditure. Although the energy expenditure aspects of such exercise may contribute to the effects of weight loss, the effect of exercise on the control of energy intake remains unclear. To evaluate the impact of physical activity on food consumption, we measured the 12-h total energy intake in lean and diet-induced obese (DIO) rats after one bout of swimming (SW Exe) and treadmill running (TR Exe) exercise. Neither of the exercise protocols changed the energy intake in lean animals; however, exercise suppressed the hyperphagic response, mediated by chronic overnutrition, restoring the energy intake to the levels of lean animals (Figure 1A). To assess whether the effects of exercise on food intake are dependent on the neuropeptides modulation, we performed a real time PCR assay to determine the mRNA levels of Neuropeptide-Y (NPY) and Proopiomelanocortin (POMC). After 9 h of fasting, we found that chronic overnutrition increased NPY mRNA and reduced POMC mRNA levels, while physical activity restored the NPY (Figure 1B) and POMC mRNA levels (Figure 1C) in obese animals; on the other hand, exercise did not change the NPY and POMC mRNA levels in lean rats (Figure 1B and C).

Bottom Line: Overnutrition caused by overeating is associated with insulin and leptin resistance through IKKbeta activation and endoplasmic reticulum (ER) stress in the hypothalamus.This molecular mechanism, mediated by physical activity, involves the anti-inflammatory protein IL-10, a core inhibitor of IKKbeta/NF-kappaB signaling and ER stress.Hence, inflammatory signaling in the hypothalamus links beneficial physiological effects of exercise to the central action of insulin and leptin.

View Article: PubMed Central - PubMed

Affiliation: Department of Internal Medicine, Faculty of Medical Sciences, State University of Campinas (UNICAMP), Campinas, São Paulo, Brazil.

ABSTRACT
Overnutrition caused by overeating is associated with insulin and leptin resistance through IKKbeta activation and endoplasmic reticulum (ER) stress in the hypothalamus. Here we show that physical exercise suppresses hyperphagia and associated hypothalamic IKKbeta/NF-kappaB activation by a mechanism dependent upon the pro-inflammatory cytokine interleukin (IL)-6. The disruption of hypothalamic-specific IL-6 action blocked the beneficial effects of exercise on the re-balance of food intake and insulin and leptin resistance. This molecular mechanism, mediated by physical activity, involves the anti-inflammatory protein IL-10, a core inhibitor of IKKbeta/NF-kappaB signaling and ER stress. We report that exercise and recombinant IL-6 requires IL-10 expression to suppress hyperphagia-related obesity. Moreover, in contrast to control mice, exercise failed to reverse the pharmacological activation of IKKbeta and ER stress in C3H/HeJ mice deficient in hypothalamic IL-6 and IL-10 signaling. Hence, inflammatory signaling in the hypothalamus links beneficial physiological effects of exercise to the central action of insulin and leptin.

Show MeSH
Related in: MedlinePlus