Increased expression of receptors for orexigenic factors in nodose ganglion of diet-induced obese rats

Paulino, Gabriel; Serre, Claire B. de La; Oort, Pieter J.; Newman, John W.; Adams, Sean H.; Raybould, Helen E.

doi:10.1152/ajpendo.90796.2008

Cited by 80 publications

(82 citation statements)

References 26 publications

(34 reference statements)

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“…A previous study in our laboratory found no significant difference in the gene expression of the leptin receptor (Ob1R) between LF, DR, or DIO rats (32). Therefore, decreased Ob1R levels are unlikely to explain the reduction in leptin signaling in the VAN of DIO rats.…”

Section: Discussionmentioning

confidence: 78%

Diet-induced obesity leads to the development of leptin resistance in vagal afferent neurons

Lartigue

Serre

Espero

et al. 2011

American Journal of Physiology-Endocrinology and Metabolism

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de Lartigue G, Barbier de la Serre C, Espero E, Lee J, Raybould HE. Diet-induced obesity leads to the development of leptin resistance in vagal afferent neurons. Am J Physiol Endocrinol Metab 301: E187-E195, 2011. First published April 26, 2011; doi:10.1152/ajpendo.00056.2011.-Ingestion of high-fat, high-calorie diets is associated with hyperphagia, increased body fat, and obesity. The mechanisms responsible are currently unclear; however, altered leptin signaling may be an important factor. Vagal afferent neurons (VAN) integrate signals from the gut in response to ingestion of nutrients and express leptin receptors. Therefore, we tested the hypothesis that leptin resistance occurs in VAN in response to a high-fat diet. Sprague-Dawley rats, which exhibit a bimodal distribution of body weight gain, were used after ingestion of a high-fat diet for 8 wk. Body weight, food intake, and plasma leptin levels were measured. Leptin signaling was determined by immunohistochemical localization of phosphorylated STAT3 (pSTAT3) in cultured VAN and by quantifaction of pSTAT3 protein levels by Western blot analysis in nodose ganglia and arcuate nucleus in vivo. To determine the mechanism of leptin resistance in nodose ganglia, cultured VAN were stimulated with leptin alone or with lipopolysaccharide (LPS) and SOCS-3 expression measured. SOCS-3 protein levels in VAN were measured by Western blot following leptin administration in vivo. Leptin resulted in appearance of pSTAT3 in VAN of low-fat-fed rats and rats resistant to diet-induced obesity but not diet-induced obese (DIO) rats. However, leptin signaling was normal in arcuate neurons. SOCS-3 expression was increased in VAN of DIO rats. In cultured VAN, LPS increased SOCS-3 expression and inhibited leptin-induced pSTAT3 in vivo. We conclude that VAN of diet-induced obese rats become leptin resistant; LPS and SOCS-3 may play a role in the development of leptin resistance.lipopolysaccharide; high-fat diet; suppressor of cytokine signaling-3 THE GUT PLAYS A CRUCIAL ROLE in sensing luminal contents that is important for the efficient digestion and absorption of ingested nutrients but also in integration of other physiological processes that regulate metabolism and energy expenditure, such as pancreatic ␤-cell function, hepatic function, and also food intake (34). In response to the presence or absence of food, enteroendocrine cells of the gut release anorexic or orexigenic hormones, respectively. The first site of integration of these signals occurs at the level of vagal afferent neurons (VAN), which project to and stimulate second-order neurons in the dorsal vagal complex of the hindbrain (27). VAN express receptors for many of the anorexigenic and orexigenic hormones released from the gut wall and mediate changes in gastrointestinal function and food intake in response to luminal nutrients (18).Leptin is a gut and adipose tissue-derived hormone that regulates a range of biological functions and processes, including energy intake and expenditure, body fat, neuroendocrine systems...

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Section: Discussionmentioning

confidence: 78%

Diet-induced obesity leads to the development of leptin resistance in vagal afferent neurons

Lartigue

Serre

Espero

et al. 2011

American Journal of Physiology-Endocrinology and Metabolism

Self Cite

152

142

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“…Direct morphological evidence identified that GHS-R1a was produced in the stomach-projected afferent neurons of the nodose ganglion in rats, suggesting that ghrelin signals from the stomach are transmitted to the brain via vagal afferent nerves (Sakata et al, 2003). Obesity-prone rats fed a high-fat diet had increased body weight, increased adiposity, and increased mRNA expression of GHS-R1a and CB 1 -R in the nodose ganglion compared with low-fat diet-fed control rats or high-fat diet-induced obesity-resistant rats (Paulino et al, 2009), demonstrating that shifts in the balance between orexigenic and anorexigenic signals within the vagal afferent pathway might influence food intake and body weight gain induced by high-fat diet.…”

Section: Normal Physiology Expression and Regulation Of Growth Hmentioning

confidence: 98%

Ghrelin Gene Products and the Regulation of Food Intake and Gut Motility

et al. 2009

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“…They may also act in the periphery to indirectly alter food intake, insulin secretion, gastric emptying, fuel utilization, and energy expenditure (14,203,249,255). Less is known about vagal afferent signals and a large number of other humoral factors known to regulate appetite and energy balance (88,178), as they have yet to be studied in the obese after weight loss or during weight regain (Fig. 3, A and B).…”

Section: The Gut: Sensing the Prandial Statementioning

confidence: 99%

Biology's response to dieting: the impetus for weight regain

MacLean

Bergouignan

Cornier

et al. 2011

American Journal of Physiology-Regulatory, Integrative and Comp

369

326

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Dieting is the most common approach to losing weight for the majority of obese and overweight individuals. Restricting intake leads to weight loss in the short term, but, by itself, dieting has a relatively poor success rate for long-term weight reduction. Most obese people eventually regain the weight they have worked so hard to lose. Weight regain has emerged as one of the most significant obstacles for obesity therapeutics, undoubtedly perpetuating the epidemic of excess weight that now affects more than 60% of U.S. adults. In this review, we summarize the evidence of biology's role in the problem of weight regain. Biology's impact is first placed in context with other pressures known to affect body weight. Then, the biological adaptations to an energy-restricted, low-fat diet that are known to occur in the overweight and obese are reviewed, and an integrative picture of energy homeostasis after long-term weight reduction and during weight regain is presented. Finally, a novel model is proposed to explain the persistence of the "energy depletion" signal during the dynamic metabolic state of weight regain, when traditional adiposity signals no longer reflect stored energy in the periphery. The preponderance of evidence would suggest that the biological response to weight loss involves comprehensive, persistent, and redundant adaptations in energy homeostasis and that these adaptations underlie the high recidivism rate in obesity therapeutics. To be successful in the long term, our strategies for preventing weight regain may need to be just as comprehensive, persistent, and redundant, as the biological adaptations they are attempting to counter. energy restriction; diet-induced obesity; obesity prone; weight loss; energy balance IN THE UNITED STATES, OVER 60% of adults and close to 20% of children are overweight or obese (35,174). A number of effective weight loss strategies are available, but most are only transiently effective over a period of 3 to 6 mo. Less than 20% of individuals that have attempted to lose weight are able to achieve and maintain a 10% reduction over a year (128). Over one-third of lost weight tends to return within the first year, and the majority is gained back within 3 to 5 years (3,246). A number of reasons have been proposed for the high incidence of weight regain (69,246), and several point to the biological response to weight loss.The objective of this review is to examine the role of this biological response in the process of weight regain. Biological regulation is first discussed in relation to other nonbiological pressures that affect body weight as weight is gained, lost, and regained. The specific biological adaptations to the most common form of dieting, an energy-restricted low-fat diet, are then discussed in more detail. Previous reviews provide extensive descriptions of the normal adaptive response to energy restriction. We do not attempt to recapitulate those efforts here. Rather, the unique perspective of this review summarizes those adaptations that have been confirmed o...

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Increased expression of receptors for orexigenic factors in nodose ganglion of diet-induced obese rats

Cited by 80 publications

References 26 publications

Diet-induced obesity leads to the development of leptin resistance in vagal afferent neurons

Diet-induced obesity leads to the development of leptin resistance in vagal afferent neurons

Ghrelin Gene Products and the Regulation of Food Intake and Gut Motility

Biology's response to dieting: the impetus for weight regain

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