scholarly journals Intermittent Fasting Promotes Fat Loss With Lean Mass Retention, Increased Hypothalamic Norepinephrine Content, and Increased Neuropeptide Y Gene Expression in Diet-Induced Obese Male Mice

Endocrinology ◽  
2015 ◽  
Vol 157 (2) ◽  
pp. 679-691 ◽  
Author(s):  
Juliet D. Gotthardt ◽  
Jessica L. Verpeut ◽  
Bryn L. Yeomans ◽  
Jennifer A. Yang ◽  
Ali Yasrebi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Weight Loss ◽  
Neuropeptide Y ◽  
Lean Mass ◽  
Area Under The Curve ◽  
Intermittent Fasting ◽  
Oral Glucose ◽  
Tissue Homogenates ◽  
Ad Libitum ◽  
The Imf

Abstract Clinical studies indicate alternate-day, intermittent fasting (IMF) protocols result in meaningful weight loss in obese individuals. To further understand the mechanisms sustaining weight loss by IMF, we investigated the metabolic and neural alterations of IMF in obese mice. Male C57/BL6 mice were fed a high-fat diet (HFD; 45% fat) ad libitum for 8 weeks to promote an obese phenotype. Mice were divided into four groups and either maintained on ad libitum HFD, received alternate-day access to HFD (IMF-HFD), and switched to ad libitum low-fat diet (LFD; 10% fat) or received IMF of LFD (IMF-LFD). After 4 weeks, IMF-HFD (∼13%) and IMF-LFD (∼18%) had significantly lower body weights than the HFD. Body fat was also lower (∼40%–52%) in all diet interventions. Lean mass was increased in the IMF-LFD (∼12%–13%) compared with the HFD and IMF-HFD groups. Oral glucose tolerance area under the curve was lower in the IMF-HFD (∼50%), whereas the insulin tolerance area under the curve was reduced in all diet interventions (∼22%–42%). HPLC measurements of hypothalamic tissue homogenates indicated higher (∼55%–60%) norepinephrine (NE) content in the anterior regions of the medial hypothalamus of IMF compared with the ad libitum-fed groups, whereas NE content was higher (∼19%–32%) in posterior regions in the IMF-LFD group only. Relative gene expression of Npy in the arcuate nucleus was increased (∼65%–75%) in IMF groups. Our novel findings indicate that intermittent fasting produces alterations in hypothalamic NE and neuropeptide Y, suggesting the counterregulatory processes of short-term weight loss are associated with an IMF dietary strategy.

scholarly journals The SLC16A11 Risk Haplotype for Type 2 Diabetes (T2D) Is Associated to Differentiated Responses in Weight Loss, and Glucose Metabolism After Treatments to Prevent T2D

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 1275-1275
Author(s):  
Magdalena Sevilla ◽  
Donaji Gomez-Velasco ◽  
Ivette Cruz-Bautista ◽  
Laura Lazaro-Carrera ◽  
Paloma Almeda-Valdes ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Weight Loss ◽  
Area Under The Curve ◽  
Postprandial Glucose ◽  
Tolerance Test ◽  
Oral Glucose ◽  
Prolonged Release ◽  
Risk Haplotype ◽  
The Impact

Abstract Objectives A haplotype in SLC16A11 is associated with decreased insulin action, and risk for type 2 diabetes (T2D) in Mexicans. We aim to determine the impact of the risk haplotype on SLC16A11 on early therapeutic responses in treatments to prevent T2D. Methods We recruited subjects with at least one prediabetes criteria according to the American Diabetes Association, and body mass index 25–45 kg/m2. Subjects were randomized in two groups: lifestyle intervention (LSI): hypocaloric diet, 25 kcal/kg of ideal weight, 45% of the total intake of carbohydrates, 30% lipids and 15% protein sources + physical activity (>150 min medium intensity per week), or LSI + metformin (750 mg prolonged release twice a day). Interventions were prescribed by standardized dietitians. The goal was to achieve >3% weight loss. We evaluated the early treatment response in a follow-up period of 12 weeks with intermediate visits each 3 weeks to reinforce knowledge and treatment goals. Evaluations (baseline and post-treatment) included an oral glucose tolerance test (OGTT), and dual-energy X-ray absorptiometry. Adherence to treatment was measured trough electronic recordings. Participants were genotyped for the risk allele rs13342232. Researchers remained blinded to the genotype results. The effects of the risk haplotype were evaluated with linear and logistic regressions adjusted by age, sex, and baseline body fat %. Results We evaluated 61 subjects, 30 carriers, and 31 non-carriers. Most of participants (57%) achieved ≥3% weight loss. The LSI + metformin treatment increased in carriers, 2 times OR 3 IC95% (1.07 – 8.6) (P = 0.04) the probability to reach the ≥3% weight loss goal compared with LSI and non-carriers. In the same treatment, carriers had a greater decrease in the total and incremental area under the curve of insulin in the OGTT IC95% (−1.75 −0.11) (P = 0.02) compared with non-carriers and LSI. Carriers also had higher decrease in postprandial glucose compared with non-carriers regardless of treatment −12.63 + 30.38 vs 0.71 30.24 (P = 0.02). Conclusions After 12 weeks of treatment, carriers with prediabetes showed a higher probability achieve weight loss and to improve insulin secretion with metformin. Regardless of the treatment, carriers were prone to improve postprandial glucose. Funding Sources Miguel Aleman Medical Research Award.

Hypothalamic neuropeptide gene expression during recovery from food restriction superimposed on short-day photoperiod-induced weight loss in the Siberian hamster

2007 ◽  
Vol 293 (3) ◽  
pp. R1094-R1101 ◽  
Author(s):  
Zoë A. Archer ◽  
Kim M. Moar ◽  
Tracy J. Logie ◽  
Laura Reilly ◽  
Valerie Stevens ◽  
...  
Keyword(s):  
Gene Expression ◽  
Weight Loss ◽  
Energy Balance ◽  
Neuropeptide Y ◽  
Caloric Restriction ◽  
Neurotrophic Factor ◽  
Food Restriction ◽  
Brain Derived Neurotrophic Factor ◽  
Related Peptide ◽  
Short Day

Previously, 40% food restriction of male Siberian hamsters over 21 days in short-day (SD) photoperiod induced characteristic changes in expression of hypothalamic arcuate nucleus energy balance genes; mRNAs for neuropeptide Y, agouti-related peptide, and leptin receptor were upregulated, and those of proopiomelanocortin and cocaine- and amphetamine-regulated transcript were depressed. The present study examined the effect of refeeding hamsters for 6 days (∼50% recovery of weight differential) or 19 days (resumption of appropriate weight trajectory). Hyperphagia continued throughout refeeding, but differences in fat pad weights and leptin levels had disappeared after 19 days. Cocaine- and amphetamine-regulated transcript gene expression was depressed by prior restriction in both refed groups. The depressive effect of prior restriction on proopiomelanocortin gene expression had disappeared after 19 days of refeeding. There was no effect of prior food restriction on neuropeptide Y or agouti-related peptide gene expression. Expression of the anorexigenic brain-derived neurotrophic factor was downregulated in the ventromedial nucleus after SD exposure for 12 wk. In the SD food restriction study, there were effects of photoperiod on brain-derived neurotrophic factor gene expression but not of prior food restriction. Hypothalamic energy balance genes in the hamster respond asynchronously to return to a seasonally appropriate body weight. The achievement of this weight rather than the weight at which caloric restriction was imposed is the critical factor. The differential responses of hypothalamic energy balance genes to food restriction and refeeding are poorly characterized in any species, a critical issue given their potential relevance to human weight loss strategies that involve caloric restriction.

scholarly journals Effect of Time-Restricted Feeding on Body Weight and Cardiometabolic Risks: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A8-A9
Author(s):  
Darin Ruanpeng ◽  
Sikarin Upala ◽  
Anawin Sanguankeo
Keyword(s):  
Systematic Review ◽  
Weight Loss ◽  
Fat Mass ◽  
Lean Mass ◽  
Meta Analysis ◽  
Control Diet ◽  
Intermittent Fasting ◽  
Randomized Controlled ◽  
Total Fat ◽  
And Control

Abstract Introduction: Time-restricted eating (TRE) or time-restricted feeding (TRF), a form of intermittent fasting (IF) when food consumption is restricted to a 4–12 hour window, poses unique possible health benefits that allow the nutrient to work in harmony with circadian rhythm. Whether TRF is effective in weight loss and cardiometabolic profile compare to usual diet is controversial. We conducted a meta-analysis of randomized control trials to investigate the weight and metabolic effects of TRF in humans. Methods: The systematic review was conducted according to the PRISMA guidelines. The literature search was conducted in MEDLINE, EMBASE, and CENTRAL from database inception to November 30, 2020. The search terms included time restricting feeding, time-restricted eating, periodic fasting, intermittent fasting, and periodic fasting. The eligibility criteria included a randomized controlled trial (RCT) comparing the effect of TRF as an intervention and control diet on weight and cardiometabolic risks in individuals with overweight (BMI 23–26.9 kg/m2 in Asian and 25–29.9 kg/m2 in others) or obesity (BMI≥27 kg/m2 in Asian and ≥30 kg/m2 in others) with study duration of at least 8 weeks. The primary outcome is the change in body weight between preintervention and postintervention. The secondary outcome is the change in total fat mass and lean mass, HDL, LDL, and triglycerides. Pool mean differences (MD) with 95% confidence interval (CI) were calculated for each outcome. Results: Four articles met the inclusion criteria and were included in this systematic review and meta-analysis. There were 511 participants with BMI 24 kg/m2 and above and aged between 18 and 65. TRF was defined as a 4–8 hours ad-lib unrestricted eating in 24 hours. The control diet was defined as ad-lib eating per usual habits. There was a significant improvement in weight and body composition in the TRF group. The mean weight loss was -2.08 kg (95% CI: -3.49 to -0.68) greater among TRF group. There was a significant total fat mass and lean mass loss in the TRF group with the MD of -1.29 kg (95% CI: -2.04 to -0.54) and -0.59 kg (95% CI: -1.15 to -0.03), respectively. There was no significant change in HDL, LDL, or triglycerides comparing between TRF and control diet. Conclusion: This systematic review and meta-analysis of RCT showed that TRF with no calories restriction resulted in significant decreased in weight, fat mass, and a slight decreased in total lean mass compared with control diet. Our findings support TRF as an effective lifestyle intervention for weight loss.

scholarly journals Effects of multiple cycles of weight loss and regain on the body weight regulatory system in rats

2019 ◽  
Vol 317 (5) ◽  
pp. E863-E870 ◽  
Author(s):  
Jennifer L. Rosenbaum ◽  
R. Scott Frayo ◽  
Susan J. Melhorn ◽  
David E. Cummings ◽  
Ellen A. Schur
Keyword(s):  
Weight Loss ◽  
Body Weight ◽  
Glucose Tolerance ◽  
Regulatory System ◽  
The Body ◽  
Oral Glucose ◽  
Positive Effects ◽  
Multiple Cycles ◽  
Ad Libitum ◽  
Ad Libitum Feeding

We studied the effects of multiple cycles of weight loss and regain on the defended body weight in rats. Thirty-six male Wistar rats were divided into three weight-matched groups: weight cyclers ( n = 18), ad libitum-fed controls ( n = 9), and maturity controls ( n = 9). Cyclers underwent four rounds of 20% weight loss from 50% caloric restriction, each cycle followed by recovery to stable plateau weight on ad libitum feeding. Controls ate ad libitum. Maturity controls ate ad libitum and then weight cycled the final two rounds to evaluate the effect of age in later cycles. Cyclers’ postdiet plateau weight became progressively lower than that of controls. With each weight loss, ghrelin increased, while insulin and leptin decreased; the magnitude of these changes did not differ across cycles. After four rounds, cyclers’ weight (504 ± 7 vs. 540 ± 22 g; P < 0.05) and percent body fat (11.7 vs. 15.2%; P < 0.05) were lower than in controls. After a 4-mo follow-up period of ad libitum feeding, cyclers maintained a lower total fat-pad mass versus controls (8.6 ± 0.5 vs. 15.9 ± 3.6 g; P < 0.01) and a lower glucose area-under-the-curve on oral glucose tolerance tests ( P < 0.05). Repeated weight-loss cycles exerted positive effects, durably lowering defended levels of body adiposity and improving glucose tolerance.

scholarly journals Experimental Hyperthyroidism Decreases Gene Expression and Serum Levels of Adipokines in Obesity

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Renata de Azevedo Melo Luvizotto ◽  
André Ferreira do Nascimento ◽  
Maria Teresa de Síbio ◽  
Regiane Marques Castro Olímpio ◽  
Sandro José Conde ◽  
...  
Keyword(s):  
Gene Expression ◽  
Weight Loss ◽  
Adipose Tissue ◽  
Serum Concentration ◽  
Serum Levels ◽  
Fat Deposits ◽  
Ad Libitum ◽  
The Relationship ◽  
Hypercaloric Diet ◽  
Gene Expression Levels

Aims. To analyze the influence of hyperthyroidism on the gene expression and serum concentration of leptin, resistin, and adiponectin in obese animals.Main Methods. MaleWistarrats were randomly divided into two groups: control (C)—fed with commercial chow ad libitum—and obese (OB)—fed with a hypercaloric diet. After group characterization, the OB rats continued receiving a hypercaloric diet and were randomized into two groups: obese animals (OB) and obese with 25 μg triiodothyronine (T3)/100 BW (OT). The T3dose was administered every day for the last 2 weeks of the study. After 30 weeks the animals were euthanized. Samples of blood and adipose tissue were collected for biochemical and hormonal analyses as well as gene expression of leptin, resistin, and adiponectin.Results. T3treatment was effective, increasing fT3levels and decreasing fT4and TSH serum concentration. Administration of T3promotes weight loss, decreases all fat deposits, and diminishes serum levels of leptin, resistin, and adiponectin by reducing their gene expression.Conclusions. Our results suggest that T3modulate serum and gene expression levels of leptin, resistin, and adiponectin in experimental model of obesity, providing new insights regarding the relationship between T3and adipokines in obesity.

scholarly journals Effects of a High-Protein/Moderate-Carbohydrate Diet on Appetite, Gut Peptides, and Endocannabinoids—A Preview Study

Nutrients ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 2269 ◽  
Author(s):  
Lea Tischmann ◽  
Mathijs Drummen ◽  
Blandine Gatta-Cherifi ◽  
Anne Raben ◽  
Mikael Fogelholm ◽  
...  
Keyword(s):  
Weight Loss ◽  
Food Intake ◽  
Weight Maintenance ◽  
Area Under The Curve ◽  
High Protein ◽  
Model Assessment ◽  
Gut Peptides ◽  
Chamber Study ◽  
Ad Libitum ◽  
Glucagon Like Peptide 1

Favorable effects of a high-protein/moderate-carbohydrate (HP/MCHO) diet after weight loss on body weight management have been shown. To extend these findings, associations between perception of hunger and satiety with endocannabinoids, and with glucagon-like peptide-1 (GLP-1) and polypeptide YY (PYY) were assessed. At approximately 34 months after weight loss, 22 female and 16 male participants (mean age 64.5 ± 5.9 years; body mass index (BMI) 28.9 ± 3.9 kg/m2) completed a 48 h respiration chamber study. Participants were fed in energy balance with a HP/MCHO diet with 25%:45%:30% or a moderate-protein/high-carbohydrate (MP/HCHO) diet with 15%:55%:30% of energy from protein:carbohydrate:fat. Endocannabinoids and related compounds, relevant postprandial hormones (GLP-1, PYY), hunger, satiety, and ad libitum food intake were assessed. HP/MCHO versus MP/HCHO reduced hunger perception. The lower decremental area under the curve (dAUC) for hunger in the HP/MCHO diet (−56.6% compared to MP, p < 0.05) was associated with the higher AUC for 2-arachidonoylglycerol (2-AG) concentrations (p < 0.05). Hunger was inversely associated with PYY in the HP/MCHO group (r = −0.7, p < 0.01). Ad libitum food intake, homeostatic model assessment for insulin resistance (HOMA-IR) and incremental AUCs for gut peptides were not different between conditions. HP/MCHO versus MP/HCHO diet-induced reduction in hunger was present after 34 months weight maintenance in the post-obese state. HP/MCHO diet-induced decrease of hunger is suggested to interact with increased 2-AG and PYY concentrations.

scholarly journals Anorectic Effects of the Cytokine, Ciliary Neurotropic Factor, Are Mediated by Hypothalamic Neuropeptide Y: Comparison with Leptin*

Endocrinology ◽  
1998 ◽  
Vol 139 (2) ◽  
pp. 466-473 ◽  
Author(s):  
B. Xu ◽  
M. G. Dube ◽  
P. S. Kalra ◽  
W. G. Farmerie ◽  
A. Kaibara ◽  
...  
Keyword(s):  
Gene Expression ◽  
Weight Loss ◽  
Body Weight ◽  
Food Intake ◽  
Neuropeptide Y ◽  
Messenger Rna ◽  
Nervous System Development ◽  
Ribonuclease Protection Assay ◽  
Dependent Manner ◽  
Neurotropic Factor

Abstract Although ciliary neurotropic factor (CNTF) is a tropic factor in nervous system development and maintenance, peripheral administration of this cytokine also causes severe anorexia and weight loss. The neural mechanism(s) mediating the loss of appetite is not known. As hypothalamic neuropeptide Y (NPY) is a potent orexigenic signal, we tested the hypothesis that CNTF may adversely affect NPYergic signaling in the hypothalamus. Intraperitoneal administration of CNTF (250μ g/kg) daily for 4 days significantly suppressed 24-h food intake in a time-dependent manner and decreased body weight. The loss in body weight was similar to that which occurred in pair-fed (PF) rats. As expected, hypothalamic NPY gene expression, determined by measurement of steady state prepro-NPY messenger RNA by ribonuclease protection assay, significantly increased in PF rats in response to energy imbalance. However, despite a similar loss in body weight, there was no increase in NPY gene expression in CNTF-treated rats. Daily administration of CNTF intracerebroventricularly (0.5 or 5.0 μg/rat) also produced anorexia and body weight loss. In this experiment, negative energy balance produced by both PF and food deprivation augmented hypothalamic NPY gene expression. However, despite reduced intake and loss of body weight, no similar increment in hypothalamic NPY gene expression was observed in CNTF-treated rats. In fact, in rats treated with higher doses of CNTF (5.0 μg/rat), NPY gene expression was reduced below the levels seen in control, freely fed rats. Furthermore, CNTF treatment also markedly decreased NPY-induced feeding. These results suggested that anorexia in CNTF-treated rats may be due to a deficit in NPY supply and possibly in the release and suppression of NPY-induced feeding. The possibility that CNTF-induced anorexia may be caused by increased leptin was next examined. Daily intracerebroventricular injections of leptin (7 μg/rat) decreased food intake, body weight, and hypothalamic NPY gene expression in a manner similar to that seen after CNTF treatment. Leptin administration also suppressed NPY-induced feeding. However, peripheral and central CNTF injections markedly decreased leptin messenger RNA in lipocytes, indicating a deficiency of leptin in these rats; thus, leptin was unlikely to be involved in appetite suppression. Thus, these results show that a two-pronged central action of CNTF, causing diminution in both NPY availability and the NPY-induced feeding response, may underlie the severe anorexia. Further, unlike other members of the cytokine family, suppression of NPYergic signaling in the hypothalamus by CNTF does not involve up-regulation of leptin, but may involve a direct action on hypothalamic NPY neurons or on neural circuits that regulate NPY signaling in the hypothalamus.

Parasite-induced anorexia: leptin, insulin and corticosterone responses to infection with the nematode, Nippostrongylus brasiliensis

Parasitology ◽  
1999 ◽  
Vol 118 (1) ◽  
pp. 117-123 ◽  
Author(s):  
H. C. ROBERTS ◽  
L. J. HARDIE ◽  
L. H. CHAPPELL ◽  
J. G. MERCER
Keyword(s):  
Gene Expression ◽  
Energy Balance ◽  
Neuropeptide Y ◽  
Post Infection ◽  
Plasma Insulin ◽  
Negative Energy ◽  
Nippostrongylus Brasiliensis ◽  
Corticotrophin Releasing Factor ◽  
Ad Libitum ◽  
Plasma Leptin

The nematode parasite, Nippostrongylus brasiliensis, induces a biphasic anorexia in its rat host. The mechanisms, underlying this anorexia and its possible advantages to the host or parasite are unknown. We have investigated the effect of acute (12–24 h) and chronic (2–17 days) infections on plasma concentrations of leptin, insulin and corticosterone, and on hypothalamic expression of neuropeptide Y, galanin and corticotrophin-releasing factor genes. Plasma leptin was elevated in infected rats relative to uninfected ad libitum-fed controls and pair-fed controls in 12 h infections initiated at dark onset and in infections of 2 days' duration. At other times prior to parasite expulsion, plasma leptin in infected and pair-fed rats was lower than that of uninfected ad libitum-fed controls, reflecting the existing state of negative energy balance. Elevated plasma leptin concentrations in infected rats at day 2 post-infection were accompanied by reduced neuropeptide Y gene expression in the hypothalamic arcuate nucleus compared with both ad libitum control and pair-fed animals, and by lowered corticotrophin-releasing factor gene expression in the paraventricular nucleus relative to pair-feds. Twelve hour infections were characterized by a substantial increase in plasma corticosterone that was independent of reduced food intake, and in 12 h infections initiated at dark onset, where plasma leptin was elevated, there was also increased plasma insulin concentration in infected rats. In longer infections, differences between the groups in plasma insulin and corticosterone concentration were only observed at day 4 post-infection. In summary, perturbations to leptin, insulin and corticosterone signals early in infection may have a causative role and might feed back onto hypothalamic gene expression, whereas subsequent changes in these parameters are more likely to be secondary to negative energy balance.

scholarly journals Stimulated Insulin Secretion Predicts Changes in Body Composition Following Weight Loss in Adults with High BMI

2021 ◽  
Author(s):  
Julia M W Wong ◽  
Shui Yu ◽  
Clement Ma ◽  
Tapan Mehta ◽  
Stephanie L Dickinson ◽  
...  
Keyword(s):  
Weight Loss ◽  
Body Composition ◽  
Insulin Secretion ◽  
Lean Mass ◽  
Linear Models ◽  
Obesity Treatment ◽  
Oral Glucose ◽  
Low Carbohydrate ◽  
Composition Changes ◽  
High Bmi

ABSTRACT Background The aim of obesity treatment is to promote loss of fat relative to lean mass. However, body composition changes with calorie restriction differ among individuals. Objectives The goal of this study was to test the hypothesis that insulin secretion predicts body composition changes among young and middle-age adults with high BMI (in kg/m2) following major weight loss. Methods Exploratory analyses were conducted with pre-randomization data from 2 large feeding trials: the Framingham, Boston, Bloomington, Birmingham, and Baylor study (FB4; n = 82, 43.9% women, BMI ≥27) and the Framingham State Food Study [(FS)2; n = 161, 69.6% women, BMI ≥25]. Participants in the 2 trials consumed calorie-restricted moderate-carbohydrate or very-low-carbohydrate diets to produce 12–18% weight loss in ∼14 wk or 10–14% in ∼10 wk, respectively. We determined insulin concentration 30 min after a 75-g oral glucose load (insulin-30) as a measure of insulin secretion and HOMA-IR as a measure of insulin resistance at baseline. Body composition was determined by DXA at baseline and post–weight loss. Associations were analyzed using general linear models with adjustment for covariates. Results In FB4, higher insulin-30 was associated with a smaller decrease in fat mass (0.441 kg per 100 μIU/mL increment in baseline insulin-30; P = 0.005; –1.20-kg mean difference between the first compared with the fifth group of insulin-30) and a larger decrease in lean mass (–0.465 kg per 100 μIU/mL; P = 0.004; 1.27-kg difference). Participants with higher insulin-30 lost a smaller proportion of weight loss as fat (–3.37% per 100 μIU/mL; P = 0.003; 9.20% difference). Greater HOMA-IR was also significantly associated with adverse body composition changes. Results from (FS)2 were qualitatively similar but of a smaller magnitude. Conclusions Baseline insulin dynamics predict substantial individual differences in body composition following weight loss. These findings may inform understanding of the pathophysiological basis for weight regain and the design of more effective obesity treatment. Registered at clinicaltrials.gov as NCT03394664 and NCT02068885.

Neuropeptide Y in hypothalamic paraventricular nucleus: a center coordinating energy metabolism

1994 ◽  
Vol 266 (6) ◽  
pp. R1765-R1770 ◽  
Author(s):  
C. J. Billington ◽  
J. E. Briggs ◽  
S. Harker ◽  
M. Grace ◽  
A. S. Levine
Keyword(s):  
Gene Expression ◽  
Energy Metabolism ◽  
Neuropeptide Y ◽  
Paraventricular Nucleus ◽  
Neural Circuit ◽  
Uncoupling Protein ◽  
Brown Fat ◽  
Mrna Levels ◽  
Ad Libitum ◽  
White Fat

Intracerebroventricular injection of neuropeptide Y (NPY) has two effects on energy metabolism in addition to increased feeding: decreased brown fat thermogenesis and increased white fat lipoprotein lipase (LPL) enzymatic activity. We hypothesized that the paraventricular nucleus (PVN) of the hypothalamus is the controlling neural site for these responses. We further hypothesized that NPY stimulation at PVN would reduce gene expression for the critical brown fat thermogenic protein, uncoupling protein (UCP), and increase gene expression for the key white fat storage enzyme, LPL. In the first experiment, three groups of rats received injections every 6 h for 24 h (5 injections total) into the PVN:1) NPY (1 micrograms/1 microliters injection) and ad libitum food; 2) NPY (1 micrograms/1 microliters injection) and food restricted to control intake; 3) saline injection (1 microliter) and ad libitum food. Both NPY-treated groups showed significant reductions (P < 0.05) in brown fat UCP mRNA levels and marked stimulation of LPL mRNA levels relative to controls. In the second experiment, four groups of seven rats had NPY injected into the PVN:0 (vehicle control); 0.1 microgram; 0.5 microgram; and 1 microgram. Injections were made every 6 h for 24 h. There was a dose-related reduction in UCP mRNA produced by the NPY treatment. NPY treatment increased LPL mRNA, but a smooth dosing effect was not evident. The observation that NPY in the PVN can coordinate more than one component of energy metabolism is significant when considered with many reports of responsiveness of NPY activity in the arcuate nucleus-PVN neural circuit to perturbations of energy balance such as fasting and feeding, diabetes, and genetic obesity.(ABSTRACT TRUNCATED AT 250 WORDS)

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