Calorie restriction attenuates LPS-induced sickness behavior and shifts hypothalamic signaling pathways to an anti-inflammatory bias

MacDonald, Leslie A.; Radler, Morgan E.; Paolini, Antonio G.; Kent, Stephen

doi:10.1152/ajpregu.00057.2011

Cited by 63 publications

(54 citation statements)

References 82 publications

(141 reference statements)

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“…Therefore, at least some of the reversible obesity-induced changes in reward behaviors could be due to changes in inflammatory signaling in brain areas controlling reward functions. Such changes have been shown in the hypothalamus (47,71), hippocampus (9,81), and striatum (41,49). It will be interesting to examine such changes in inflammatory signaling in other key structures controlling reward functions, such as the nucleus accumbens, ventral tegmental area, and orbitofrontal cortex.…”

Section: Perspectives and Significancementioning

confidence: 95%

“Liking” and “wanting” of sweet and oily food stimuli as affected by high-fat diet-induced obesity, weight loss, leptin, and genetic predisposition

Shin

Townsend

Patterson

et al. 2011

American Journal of Physiology-Regulatory, Integrative and Comp

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Cross-sectional studies in both humans and animals have demonstrated associations between obesity and altered reward functions at the behavioral and neural level, but it is unclear whether these alterations are cause or consequence of the obese state. Reward behaviors were quantified in male, outbred Sprague-Dawley (SD) and selected line obesity-prone (OP) and obesity-resistant (OR) rats after induction of obesity by high-fat diet feeding and after subsequent loss of excess body weight by chronic calorie restriction. As measured by the brief access lick and taste-reactivity paradigms, both obese SD and OP rats "liked" low concentrations of sucrose and corn oil less, but "liked" the highest concentrations more, compared with lean rats, and this effect was fully reversed by weight loss in SD rats. Acute food deprivation was unable to change decreased responsiveness to low concentrations but eliminated increased responsiveness to high concentrations in obese SD rats, and leptin administration in weight-reduced SD rats shifted concentration-response curves toward that seen in the obese state in the brief access lick test. "Wanting" and reinforcement learning as assessed in the incentive runway and progressive ratio lever-pressing paradigms was paradoxically decreased in both obese (compared with lean SD rats) and OP (compared with OR rats). Thus, reversible, obesity-associated, reduced "liking" and "wanting" of low-calorie foods in SD rats suggest a role for secondary effects of the obese state on reward functions, while similar differences between select lines of OP and OR rats before induction of obesity indicate a genetic component.

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Section: Perspectives and Significancementioning

confidence: 95%

“Liking” and “wanting” of sweet and oily food stimuli as affected by high-fat diet-induced obesity, weight loss, leptin, and genetic predisposition

Shin

Townsend

Patterson

et al. 2011

American Journal of Physiology-Regulatory, Integrative and Comp

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“…Williams et al (1997) similarly reported depressed feed intake in pigs reared in poor sanitary conditions when compared with those reared in good sanitary conditions. Infection-induced anorexia has been considered as part of the host non-specific immune response, which consists in reducing the availability of nutrients essential to development and growth of pathogens (Exton, 1997;MacDonald et al, 2011). In addition, anorexia seems to enhance function and proliferation of macrophages, contributing to recognition and elimination of pathogens (Exton, 1997).…”

Section: Voluntary Feed Intake and Growth Performancementioning

confidence: 99%

Physiological responses of growing pigs to high ambient temperature and/or inflammatory challenges

et al. 2017

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-Global warming is one of the major environmental threats facing the world in the 21st century. This fact will have a significant impact on pig production due to its direct effects on welfare, health, and performance of pigs. Besides, the effects of high temperatures will presumably become more important over the next decades due to the development of pig production in developing countries mainly located in tropical and subtropical areas, where animals are often exposed to ambient temperatures above their thermal comfort zone. Furthermore, pigs reared in tropical areas are often confronted to sanitary challenges including poor hygiene conditions, lack of respect for sanitary rules, and pathogens. This results in the stimulation of the immune system and, as a consequence, in the production of pro-inflammatory cytokines and neuroendocrine adjustments that, in turn, usually have a negative impact on growth and feed efficiency. Although the effects of high ambient temperature and disease on pig physiology and performance have been well documented in literature, little is known about the associated effects of both factors. This understanding may contribute to a better quantification and comprehension of the physiological and metabolic disturbances occurring in practical conditions of pig production in tropical areas and, more generally, in many other geographic areas that will be influenced by the perspective of global warming. Therefore, the objective of this work is to provide an overview of recent research advances on the physiological responses of growing pigs during acclimation to high ambient temperature and on the potential effects of high ambient temperature on the ability of growing pigs to resist, cope with, or recover from an inflammatory challenge.

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“…To the best of our knowledge, designer receptors exclusively activated by designer drug has been seldom used to investigate inflammatory anorexia (42). A unique advantage of this technique is that it allows for robust stimulation of feeding without the need for fasting of animals, which can interfere with immunity and the endocrine axis (43)(44)(45). Moreover, each mouse can be used as its own control.…”

Section: Pharmacogenetics and Brain Surgerymentioning

confidence: 99%

Lipopolysacharide Rapidly and Completely Suppresses AgRP Neuron-Mediated Food Intake in Male Mice

Liu

Huang

Liu³

et al. 2016

Endocrinology

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Although Agouti-related peptide (AgRP) neurons play a key role in the regulation of food intake, their contribution to the anorexia caused by proinflammatory insults has yet to be identified. Using a combination of neuroanatomical and pharmacogenetics experiments, this study sought to investigate the importance of AgRP neurons and downstream targets in the anorexia caused by the peripheral administration of a moderate dose of lipopolysaccharide (LPS) (100 μg/kg, ip). First, in the C57/Bl6 mouse, we demonstrated that LPS induced c-fos in select AgRP-innervated brain sites involved in feeding but not in any arcuate proopiomelanocortin neurons. Double immunohistochemistry further showed that LPS selectively induced c-Fos in a large subset of melanocortin 4 receptor-expressing neurons in the lateral parabrachial nucleus. Secondly, we used pharmacogenetics to stimulate the activity of AgRP neurons during the course of LPS-induced anorexia. In AgRP-Cre mice expressing the designer receptor hM3Dq-Gq only in AgRP neurons, the administration of the designer drug clozapine-N-oxide (CNO) induced robust food intake. Strikingly, CNO-mediated food intake was rapidly and completely blunted by the coadministration of LPS. Neuroanatomical experiments further indicated that LPS did not interfere with the ability of CNO to stimulate c-Fos in AgRP neurons. In summary, our findings combined together support the view that the stimulation of select AgRP-innervated brain sites and target neurons, rather than the inhibition of AgRP neurons themselves, is likely to contribute to the rapid suppression of food intake observed during acute bacterial endotoxemia.

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Calorie restriction attenuates LPS-induced sickness behavior and shifts hypothalamic signaling pathways to an anti-inflammatory bias

Cited by 63 publications

References 82 publications

“Liking” and “wanting” of sweet and oily food stimuli as affected by high-fat diet-induced obesity, weight loss, leptin, and genetic predisposition

“Liking” and “wanting” of sweet and oily food stimuli as affected by high-fat diet-induced obesity, weight loss, leptin, and genetic predisposition

Physiological responses of growing pigs to high ambient temperature and/or inflammatory challenges

Lipopolysacharide Rapidly and Completely Suppresses AgRP Neuron-Mediated Food Intake in Male Mice

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