Chronic consumption of a low-fat diet leads to increased hypothalamic agouti-related protein and reduced leptin

Staszkiewicz, Jarosław; Horswell, Ronald; Argyropoulos, George

doi:10.1016/j.nut.2007.06.001

Cited by 18 publications

(8 citation statements)

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“…In animal studies it has been found that high-fat diet leads to decreased expression of AgRP in the hypothalamus, probably in the mechanism moderated by leptin (Staszkiewicz et al 2007 ). We have no detailed data on diet patterns of our study subjects, but reports are consistent that patients with schizophrenia consume higher amounts of high-fat foods compared with healthy population (Dipasquale et al 2013 ).…”

Section: Discussionmentioning

confidence: 99%

Serum levels of AgRP protein in patients with schizophrenia on clozapine monotherapy

2014

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Aim: Agouti-related peptide (AgRP) is one of the hypothalamic hormones that works by increasing appetite and decreasing metabolism, thus leading to weight gain. The aim of the study was to find out if AgRP level in subjects with schizophrenia on clozapine monotherapy is higher compared with healthy controls. Methodology: We determined fasting serum AgRP levels in 24 subjects with schizophrenia on clozapine monotherapy and 24 healthy, age- and sex-matched controls. Biochemical and anthropometric measurements were combined with body composition analysis. Results: There was no difference for AgRP levels between patients taking clozapine and control group (15.00±8.65 vs. 15.33±6.82 pg/mL, p =0.37). We found negative correlations between AgRP levels and total body fat (r =−0.34 and −0.48 in the whole study group and clozapine group, respectively) and positive correlations with lean body mass (r =0.38 and 0.49 in the whole study group and clozapine group, respectively), body water (r =0.34 and 0.49 in the whole study group and clozapine group, respectively) and basal metabolic rate (r =0.42 both in the clozapine and control groups). There were no correlations with age, height, weight, body mass index, fat mass index, abdominal, waist or hip circumferences, waist-hip ratio, blood pressure, total cholesterol, HDL, LDL, triglycerides, uric acid, glucose, insulin, clozapine dose or treatment duration, duration of treatment with antipsychotics and markers for insulin resistance. Conclusion: We cannot conclude that treatment with clozapine is associated with increased level of AgRP. We did not find previously described differences in AgRP levels between obese and non-obese subjects or associations between AgRP and various metabolic parameters.

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Section: Discussionmentioning

confidence: 99%

Serum levels of AgRP protein in patients with schizophrenia on clozapine monotherapy

2014

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“…Orexigenic Npy and Agrp production is inhibited by leptin, so downregulation is the expected response. In DIO mice elevated Npy expression is usual [27,30–36] and has been cited as the reason for obesity susceptibility, but downregulation [27,29,37–39] or no change [28,30,40] has also been reported. It therefore appears that varying degrees of homeostatic efficiency by neuropeptides exist in the obesity-prone mouse model.…”

Section: Discussionmentioning

confidence: 99%

Effect of high-fat feeding on expression of genes controlling availability of dopamine in mouse hypothalamus

et al. 2010

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ObjectiveHypothalamic centers integrate external signals of nutrient availability and energy status and initiate responses to maintain homeostasis. Quantifying changes in hypothalamic gene expression in the presence of nutrient excess may identify novel responsive elements.MethodsAffymetrix Mouse Genome 430 2.0 oligonucleotide microarrays containing 45 102 probe sets were used to interrogate differential expression of genes in dietary-induced obesity model C57BL6 inbred mice fed a high-fat (35% fat; n = 8) or standard (4% fat; n = 6) diet from 3 to 15 wk of age. Ontologies of regulated genes were examined and expression of selected genes was validated by quantitative real-time polymerase chain reaction.ResultsOne thousand two hundred twelve unique gene transcripts showed altered expression on the microarrays. Gene ontology analysis revealed changes in neuropeptide genes responding to leptin, Pomc, Cart, Npy, and Agrp, compatible with a homeostatic response to high-fat intake, although mean weight increased 2.3-fold compared with standard fed mice (P < 0.001). Neurotransmitter system ontologies revealed upregulation of five genes controlling availability of dopamine. Changes in Th tyrosine hydroxylase (2.1-fold) and Slc18a2 solute carrier family 18 (vesicular monoamine), member 2 (4.4-fold) controlling synthesis and release, and Slc6a3 solute carrier family 6 (neurotransmitter transporter, dopamine), member 3 (4.8-fold), Snca α-synuclein (1.3-fold), and Maoa monoamine oxidase (1.9-fold) limiting availability were confirmed by quantitative real-time polymerase chain reaction.ConclusionExpression of five genes involved in availability of dopamine was increased after a high-fat diet. Failure to reduce dopamine availability sufficiently, to counter the feeding reward effect, could contribute to diet-induced obesity in these mice.

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“…In contrast, AgRP neurons also express receptors for ghrelin, a hunger-inducing hormone secreted by the stomach (Nakazato et al, 2001 ). In response to ghrelin and conditions of fasting, these neurons upregulate AgRP and NPY mRNA expression and increase neuronal activity (Kamegai et al, 2000 ; Nakazato et al, 2001 ; Seoane et al, 2003 ; van den Top et al, 2004 ; Takahashi and Cone, 2005 ; Staszkiewicz et al, 2007 ; Wang et al, 2014 ). Thus, AgRP neurons are primed to detect peripheral signals from the body and orchestrate a central feeding response.…”

Section: Agrp Neurons Orchestrate Food-seeking Behaviormentioning

confidence: 99%

Understanding how discrete populations of hypothalamic neurons orchestrate complicated behavioral states

Graebner

Iyer

Carter

2015

Front. Syst. Neurosci.

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A major question in systems neuroscience is how a single population of neurons can interact with the rest of the brain to orchestrate complex behavioral states. The hypothalamus contains many such discrete neuronal populations that individually regulate arousal, feeding, and drinking. For example, hypothalamic neurons that express hypocretin (Hcrt) neuropeptides can sense homeostatic and metabolic factors affecting wakefulness and orchestrate organismal arousal. Neurons that express agouti-related protein (AgRP) can sense the metabolic needs of the body and orchestrate a state of hunger. The organum vasculosum of the lamina terminalis (OVLT) can detect the hypertonicity of blood and orchestrate a state of thirst. Each hypothalamic population is sufficient to generate complicated behavioral states through the combined efforts of distinct efferent projections. The principal challenge to understanding these brain systems is therefore to determine the individual roles of each downstream projection for each behavioral state. In recent years, the development and application of temporally precise, genetically encoded tools has greatly improved our understanding of the structure and function of these neural systems. This review will survey recent advances in our understanding of how these individual hypothalamic populations can orchestrate complicated behavioral states due to the combined efforts of individual downstream projections.

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Chronic consumption of a low-fat diet leads to increased hypothalamic agouti-related protein and reduced leptin

Abstract: Dietary fat can have a tissue-dependent effect on AgRP that may be unfettered by leptin under an HFD.

Cited by 18 publications

References 48 publications

Serum levels of AgRP protein in patients with schizophrenia on clozapine monotherapy

Serum levels of AgRP protein in patients with schizophrenia on clozapine monotherapy

Effect of high-fat feeding on expression of genes controlling availability of dopamine in mouse hypothalamus

Understanding how discrete populations of hypothalamic neurons orchestrate complicated behavioral states

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