Diet-induced obesity blunts the behavioural effects of ghrelin: studies in a mouse-progressive ratio task

Finger, Beate C.; Dinan, Timothy G.; Cryan, John F.

doi:10.1007/s00213-011-2468-0

Cited by 57 publications

(45 citation statements)

References 58 publications

(85 reference statements)

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“…For example, diet-induced obesity attenuates ghrelin's ability to increase food intake (27) due to ghrelin resistance in hypothalamic NPY neurons (20). The ability of ghrelin to increase motivation in a progressive task ratio is also impaired in diet-induced obesity (28). On the other hand, fasting increases ghrelin or GHSR agonist-induced food intake and cfos activation in the arcuate nucleus (22,23) and weight loss after HFD exposure restores ghrelin sensitivity in NPY neurons (21).…”

Section: Discussionmentioning

confidence: 98%

Acyl Ghrelin Acts in the Brain to Control Liver Function and Peripheral Glucose Homeostasis in Male Mice

et al. 2015

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Recent evidence suggests that peripheral ghrelin regulates glucose metabolism. Here, we designed experiments to examine how central acyl ghrelin infusion affects peripheral glucose metabolism under pair-fed or ad libitum feeding conditions. Mice received intracerebroventricular (icv) infusion of artificial cerebrospinal fluid (aCSF), ghrelin, and allowed to eat ad libitum (icv ghrelin ad lib) or ghrelin and pair-fed to the aCSF group (icv ghrelin pf). Minipumps delivered acyl ghrelin at a dose of 0.25 μg/h at 0.5 μL/h for 7 days. There was no difference in daily blood glucose, insulin, glucagon, triglycerides, or nonesterified fatty acids. Body weight gain and food intake was significantly higher in icv ghrelin ad lib mice. However, both icv ghrelin ad lib and icv ghrelin pf groups exhibited heavier white adipose mass. Icv ghrelin pf mice exhibited better glucose tolerance than aCSF or icv ghrelin ad lib mice during a glucose tolerance test, although both icv ghrelin ad lib and icv ghrelin pf increased insulin release during the glucose tolerance test. Central acyl ghrelin infusion and pair feeding also increased breakdown of liver glycogen and triglyceride, and regulated genes involved in hepatic lipid and glucose metabolism. Icv ghrelin pf mice had an increase in plasma blood glucose during a pyruvate tolerance test relative to icv ghrelin ad lib or aCSF mice. Our results suggest that under conditions of negative energy (icv ghrelin pf), central acyl ghrelin engages a neural circuit that influences hepatic glucose function. Metabolic status affects the ability of central acyl ghrelin to regulate peripheral glucose homeostasis.

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Section: Discussionmentioning

confidence: 98%

Acyl Ghrelin Acts in the Brain to Control Liver Function and Peripheral Glucose Homeostasis in Male Mice

et al. 2015

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“…Peripheral or central ghrelin in mice promotes dopamine availability in the nucleus accumbens, while antagonism of the GHSR reduces drug-induced dopamine release (Abizaid et al, 2006;Jerlhag et al, 2007;.Therefore the inability of ghrelin to induce a CPP in HFD mice supports the idea the ghrelin resistance occurs in pathways controlling reward behaviours, including non-dopaminergic inputs. It is important to note that this is not just a phenomenon associated with specific CPP behaviour as ghrelin resistance has also been observed in operant based motivational tasks in diet-induced obese rats (Finger et al, 2012).…”

Section: Discussionmentioning

confidence: 98%

“…The interaction between HFD feeding and reward processing is as yet not well understood, however ghrelin resistance appears to extend to behavioural measures beyond feeding. In chow fed rats, ghrelin increases responding on a progressive ratio task, however it is ineffective in altering responding in obese rats (Finger et al, 2012). It is currently unclear exactly howHFD feeding effects other ghrelin-responsive cell populations, such as those in the VTA, and whether this has functional effects for mouse behaviour and reward processing.…”

Section: Introductionmentioning

confidence: 99%

Diet-induced obesity causes ghrelin resistance in reward processing tasks

Lockie

Dinan

Lawrence

et al. 2015

Psychoneuroendocrinology

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Diet-induced obesity (DIO) causes ghrelin resistance in hypothalamic Agouti-related peptide (AgRP) neurons. However, ghrelin promotes feeding through actions at both the hypothalamus and mesolimbic dopamine reward pathways. Therefore, we hypothesized that DIO would also establish ghrelin resistance in the ventral tegmental area (VTA), a major site of dopaminergic cell bodies important in reward processing. We observed reduced sucrose and saccharin consumption in Ghrelin KO vs Ghrelin WT mice. Moreover, DIO reduced saccharin consumption relative to chow-fed controls. These data suggest that the deletion of ghrelin and high fat diet both cause anhedonia. To assess if these are causally related, we tested whether DIO caused ghrelin resistance in a classic model of drug reward, conditioned place preference (CPP). Chow or high fat diet (HFD) mice were conditioned with ghrelin (1mg/kg in 10ml/kg ip) in the presence or absence of food in the conditioning chamber. We observed a CPP to ghrelin in chow-fed mice but not in HFD-fed mice. HFD-fed mice still showed a CPP for cocaine (20mg/kg), indicating that they maintained the ability to develop conditioned behaviour. The absence of food availability during ghrelin conditioning sessions induced a conditioned place aversion, an effect that was still present in both chow and HFD mice. Bilateral intra-VTA ghrelin injection (0.33μg/μl in 0.5μl) robustly increased feeding in both chow-fed and high fat diet (HFD)-fed mice; however, this was correlated with body weight only in the chow-fed mice. Our results suggest that DIO causes ghrelin resistance albeit not directly in the VTA. We suggest there is impaired ghrelin sensitivity in upstream pathways regulating reward pathways, highlighting a functional role for ghrelin linking appropriate metabolic sensing with reward processing.

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“…In humans and rodents, reward signalling is altered in obesity (Batterink et al, 2010;Burger and Stice, 2011;Finger et al, 2012;Johnson and Kenny, 2010;Shin and Berthoud, 2011;Stoeckel et al, 2008), due at least in part to chronic HFD-mediated epigenetic dysregulation of key dopaminergic and opioidergic signalling molecules (Vucetic et al, 2011(Vucetic et al, , 2012. In addition, dysregulated reward signalling may predispose to diet-induced obesity (Blum et al, 2014;Volkow et al, 2008).…”

Section: Central Control Of Food Intake: Programming the Hypothalamusmentioning

confidence: 95%

Developmental programming by maternal obesity in 2015: Outcomes, mechanisms, and potential interventions

Penfold

Ozanne

2015

Hormones and Behavior

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This article is part of a Special Issue "SBN 2014". Obesity in women of child-bearing age is a growing problem in developed and developing countries. Evidence from human studies indicates that maternal BMI correlates with offspring adiposity from an early age and predisposes to metabolic disease in later life. Thus the early life environment is an attractive target for intervention to improve public health. Animal models have been used to investigate the specific physiological outcomes and mechanisms of developmental programming that result from exposure to maternal obesity in utero. From this research, targeted intervention strategies can be designed. In this review we summarise recent progress in this field, with a focus on cardiometabolic disease and central control of appetite and behaviour. We highlight key factors that may mediate programming by maternal obesity, including leptin, insulin, and ghrelin. Finally, we explore potential lifestyle and pharmacological interventions in humans and the current state of evidence from animal models.

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Diet-induced obesity blunts the behavioural effects of ghrelin: studies in a mouse-progressive ratio task

Cited by 57 publications

References 58 publications

Acyl Ghrelin Acts in the Brain to Control Liver Function and Peripheral Glucose Homeostasis in Male Mice

Acyl Ghrelin Acts in the Brain to Control Liver Function and Peripheral Glucose Homeostasis in Male Mice

Diet-induced obesity causes ghrelin resistance in reward processing tasks

Developmental programming by maternal obesity in 2015: Outcomes, mechanisms, and potential interventions

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