Restricting feeding to dark phase fails to entrain circadian activity and energy expenditure oscillations in Pitx3-mutant Aphakia mice

The objective of this study was to determine whether the previously observed effects of photoperiod on body weight in Siberian hamsters were due to changes in the daily patterns of locomotor activity, energy expenditure, and/or feeding behavior. Adult males were monitored through a seasonal cycle using an automated comprehensive laboratory animal monitoring system (CLAMS). Exposure to a short-day photoperiod (SD; 8:16-h light-dark cycle) induced a significant decline in body weight, and oxygen consumption (V̇o2), carbon dioxide production (V̇co2), and heat production all decreased reaching a nadir by 16 wk of SD. Clear daily rhythms in locomotor activity, V̇o2, and V̇co2 were observed at the start of the study, but these all progressively diminished after prolonged exposure to SD. Rhythms in feeding behavior were also detected initially, reflecting an increase in meal frequency but not duration during the dark phase. This rhythm was lost by 8 wk of SD exposure such that food intake was relatively constant across dark and light phases. After 18 wk in SD, hamsters were transferred to a long-day photoperiod (LD; 16:8-h light-dark cycle), which induced significant weight gain. This was associated with an increase in energy intake within 2 wk, while V̇o2, V̇co2, and heat production all increased back to basal levels. Rhythmicity was reestablished within 4 wk of reexposure to long days. These results demonstrate that photoperiod impacts on body weight via complex changes in locomotor activity, energy expenditure, and feeding behavior, with a striking loss of daily rhythms during SD exposure.

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APP deficiency results in resistance to obesity but impairs glucose tolerance upon high fat feeding

Journal of Endocrinology ◽

10.1530/joe-18-0051 ◽

2018 ◽

Vol 237 (3) ◽

pp. 311-322 ◽

Cited By ~ 6

Author(s):

Juliane K Czeczor ◽

Amanda J Genders ◽

Kathryn Aston-Mourney ◽

Timothy Connor ◽

Liam G Hall ◽

...

Keyword(s):

Energy Expenditure ◽

Glucose Tolerance ◽

Cell Mass ◽

Tolerance Test ◽

Whole Body ◽

Dark Phase ◽

High Fat ◽

Neuronal Metabolism ◽

Fat Feeding ◽

Deficient Mice

The amyloid precursor protein (APP) generates a number of peptides when processed through different cleavage mechanisms, including the amyloid beta peptide that is implicated in the development of Alzheimer’s disease. It is well established that APP via its cleaved peptides regulates aspects of neuronal metabolism. Emerging evidence suggests that amyloidogenic processing of APP can lead to altered systemic metabolism, similar to that observed in metabolic disease states. In the present study, we investigated the effect of APP deficiency on obesity-induced alterations in systemic metabolism. Compared with WT littermates, APP-deficient mice were resistant to diet-induced obesity, which was linked to higher energy expenditure and lipid oxidation throughout the dark phase and was associated with increased spontaneous physical activity. Consistent with this lean phenotype, APP-deficient mice fed a high-fat diet (HFD) had normal insulin tolerance. However, despite normal insulin action, these mice were glucose intolerant, similar to WT mice fed a HFD. This was associated with reduced plasma insulin in the early phase of the glucose tolerance test. Analysis of the pancreas showed that APP was required to maintain normal islet and β-cell mass under high fat feeding conditions. These studies show that, in addition to regulating aspects of neuronal metabolism, APP is an important regulator of whole body energy expenditure and glucose homeostasis under high fat feeding conditions.

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Time-Restricted Feeding a High-fat Diet in Mice Elevates Plasma Concentration of Saturated Fatty Acids but Reduces Concentrations of Multiple Amino Acids (OR27-02-19)

Current Developments in Nutrition ◽

10.1093/cdn/nzz046.or27-02-19 ◽

2019 ◽

Vol 3 (Supplement_1) ◽

Author(s):

Bret Rust ◽

Aaron Mehus ◽

Joseph Idso ◽

Matthew Picklo

Keyword(s):

Amino Acids ◽

Fatty Acids ◽

Energy Expenditure ◽

Control Diet ◽

Saturated Fatty Acids ◽

Plasma Metabolites ◽

Dark Phase ◽

Restricted Feeding ◽

High Fat ◽

Branched Chain

Abstract Objectives Obesity and obesity-related disease contribute to health care costs and pose serious health risks. Rodent studies indicate that time-restricted feeding (TRF) may be effective in reducing adiposity and metabolic disease associated with obesity. However, the metabolic pathways impacted by TRF in the context of obesogenic, high-fat (HF) diets need clarity. In the present work we examined the metabolomic changes in plasma induced by TRF of a HF diet in mice compared to a HF diet eaten ad libitum (AL) vs AL intake of a low-fat (LF) control diet. Methods Male mice (12 weeks old) were fed a LF-AL diet (16%en fat), a HF-AL diet (48%en fat) or a HF diet restricted to feeding for 12 hours per day during the dark phase (HF-TRF). In week 9 of the study, energy expenditure data were collected. After 12 weeks, animals were fasted and plasma collected for clinical chemistries and metabolomic analysis. Multivariate analysis was used to discriminate diet treatments in untargeted metabolomic data. Results Energy expenditure measurements throughout the day showed a markedly reduced fasting respiratory exchange ratio (RER) in HF-TRF mice during the inactive (light) phase compared to AL groups. Measures of insulin resistance, while increased with HF-AL intake, were resolved in the HF-TRF group. Partial least squares discriminant analysis revealed plasma non-esterified fatty acids (NEFA) and amino acids (AA) to be important discriminators between diet treatments. TRF resulted in elevated NEFA concentrations of the saturated fatty acids (12:0 to 18:0) and the polyunsaturated fatty acids α-linolenic acid and linoleic acid compared to HF-AL. Conversely, the concentrations of aromatic and branched chain amino acids were reduced in HF-TRF mice compared to HF-AL mice. Conclusions Alterations in plasma metabolites following TRF of a HF diet are consistent with greater lipid utilization during the inactive phase as reflected in the RER. Decreases in the aromatic and branched chain amino acid concentrations are consistent with improved insulin sensitivity in humans. Funding Sources This work was supported by USDA-ARS project 3062-51000-053-00D. Supporting Tables, Images and/or Graphs

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Mice lacking melanin-concentrating hormone receptor 1 demonstrate increased heart rate associated with altered autonomic activity

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00134.2004 ◽

2004 ◽

Vol 287 (4) ◽

pp. R749-R758 ◽

Cited By ~ 64

Author(s):

Annika Åstrand ◽

Mohammad Bohlooly-Y ◽

Sara Larsdotter ◽

Margit Mahlapuu ◽

Harriet Andersén ◽

...

Keyword(s):

Heart Rate ◽

Nervous System ◽

Autonomic Nervous System ◽

Body Temperature ◽

Energy Expenditure ◽

Dark Phase ◽

Wild Type ◽

Autonomic Nervous ◽

Significant Difference ◽

Melanin Concentrating Hormone

Melanin-concentrating hormone (MCH) plays an important role in energy balance. The current studies were carried out on a new line of mice lacking the rodent MCH receptor (MCHR1−/− mice). These mice confirmed the previously reported lean phenotype characterized by increased energy expenditure and modestly increased caloric intake. Because MCH is expressed in the lateral hypothalamic area, which also has an important role in the regulation of the autonomic nervous system, heart rate and blood pressure were measured by a telemetric method to investigate whether the increased energy expenditure in these mice might be due to altered autonomic nervous system activity. Male MCHR1−/− mice demonstrated a significantly increased heart rate [24-h period: wild type 495 ± 4 vs. MCHR1−/− 561 ± 8 beats/min ( P < 0.001); dark phase: wild type 506 ± 8 vs. MCHR1−/− 582 ± 9 beats/min ( P < 0.001); light phase: wild type 484 ± 13 vs. MCHR1−/− 539 ± 9 beats/min ( P < 0.005)] with no significant difference in mean arterial pressure [wild type 110 ± 0.3 vs. MCHR1−/− 113 ± 0.4 mmHg ( P > 0.05)]. Locomotor activity and core body temperature were higher in the MCHR1−/− mice during the dark phase only and thus temporally dissociated from heart rate differences. On fasting, wild-type animals rapidly downregulated body temperature and heart rate. MCHR1−/− mice displayed a distinct delay in the onset of this downregulation. To investigate the mechanism underlying these differences, autonomic blockade experiments were carried out. Administration of the adrenergic antagonist metoprolol completely reversed the tachycardia seen in MCHR1−/− mice, suggesting an increased sympathetic tone.

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Reduced Diet-induced Thermogenesis in Apolipoprotein A-IV Deficient Mice

International Journal of Molecular Sciences ◽

10.3390/ijms20133176 ◽

2019 ◽

Vol 20 (13) ◽

pp. 3176 ◽

Cited By ~ 1

Author(s):

Sydney Pence ◽

Qi Zhu ◽

Erin Binne ◽

Min Liu ◽

Haifei Shi ◽

...

Keyword(s):

Energy Expenditure ◽

Energy Homeostasis ◽

Uncoupling Protein ◽

Dietary Lipid ◽

Dietary Lipids ◽

Chow Diet ◽

Dark Phase ◽

Apolipoprotein A ◽

Brown Adipose ◽

Diet Induced Thermogenesis

In the presence of dietary lipids, both apolipoprotein A-IV (ApoA-IV) production and brown adipose tissue (BAT) thermogenesis are increased. The effect of dietary lipid-induced AproA-IV on BAT thermogenesis and energy expenditure remains unknown. In the present study, we hypothesized that ApoA-IV knockout (ApoA-IV-KO) mice exhibited decreased BAT thermogenesis to affect energy homeostasis. To test this hypothesis, BAT thermogenesis in wildtype (WT) and ApoA-IV-KO mice fed either a standard low-fat chow diet or a high-fat diet (HFD) was investigated. When fed a chow diet, energy expenditure and food intake were comparable between WT and ApoA-IV-KO mice. After 1 week of HFD consumption, ApoA-IV-KO mice had comparable energy intake but produced lower energy expenditure relative to their WT controls in the dark phase. After an acute feeding of dietary lipids or 1-week HFD feeding, ApoA-IV-KO mice produced lower levels of uncoupling protein 1 (UCP1) and exhibited reduced expression of thermogenic genes in the BAT compared with WT controls. In response to cold exposure, however, ApoA-IV-KO mice had comparable energy expenditure and BAT temperature relative to WT mice. Thus, ApoA-IV-KO mice exhibited reduced diet-induced BAT thermogenesis and energy expenditure.

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Sex Differences in Somatotrope Dependency on Leptin Receptors in Young Mice: Ablation of LEPR Causes Severe Growth Hormone Deficiency and Abdominal Obesity in Males

Endocrinology ◽

10.1210/en.2015-1198 ◽

2015 ◽

Vol 156 (9) ◽

pp. 3253-3264 ◽

Cited By ~ 13

Author(s):

Melody L. Allensworth-James ◽

Angela Odle ◽

Anessa Haney ◽

Gwen Childs

Keyword(s):

Sex Differences ◽

Adipose Tissue ◽

Energy Expenditure ◽

Respiratory Quotient ◽

Leptin Receptor ◽

Fold Increase ◽

Hormone Deficiency ◽

Dark Phase ◽

Gh Cells ◽

Exon 1

Leptin receptor (LEPR) signaling controls appetite and energy expenditure. Somatotrope-specific deletion of the LEPRb signaling isoform causes GH deficiency and obesity. The present study selectively ablated Lepr exon 1 in somatotropes, which removes the signal peptide, causing the loss of all isoforms of LEPR. Excision of Lepr exon 1 was restricted to the pituitary, and mutant somatotropes failed to respond to leptin. Young (2–3 mo) males showed a severe 84% reduction in serum GH levels and more than 60% reduction in immunolabeled GH cells compared with 41%–42% reductions in GH and GH cells in mutant females. Mutant males (35 d) and females (45 d) weighed less than controls and males had lower lean body mass. Image analysis of adipose tissue by magnetic resonance imaging showed that young males had a 2-fold increase in abdominal fat mass and increased adipose tissue density. Young females had only an overall increase in adipose tissue. Both males and females showed lower energy expenditure and higher respiratory quotient, indicating preferential carbohydrate burning. Young mutant males slept less and were more restless during the dark phase, whereas the opposite was true of females. The effects of a Cre-bearing sire on his non-Cre-recombinase bearing progeny are seen by increased respiratory quotient and reduced litter sizes. These studies elucidate clear sex differences in the extent to which somatotropes are dependent on all isoforms of LEPR. These results, which were not seen with the ablation of Lepr exon 17, highlight the severe consequences of ablation of LEPR in male somatotropes.

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Central Injection of the Stable Somatostatin Analog ODT8-SST Induces a Somatostatin2 Receptor-Mediated Orexigenic Effect: Role of Neuropeptide Y and Opioid Signaling Pathways in Rats

Endocrinology ◽

10.1210/en.2010-0195 ◽

2010 ◽

Vol 151 (9) ◽

pp. 4224-4235 ◽

Cited By ~ 30

Author(s):

Andreas Stengel ◽

Tamer Coskun ◽

Miriam Goebel ◽

Lixin Wang ◽

Libbey Craft ◽

...

Keyword(s):

Food Intake ◽

Energy Expenditure ◽

Neuropeptide Y ◽

Receptor Antagonist ◽

Opioid Receptor ◽

Somatostatin Receptors ◽

Opiate Receptors ◽

Dark Phase ◽

Solid Meal ◽

Μ Opioid Receptor

Somatostatin and octreotide injected into the brain have been reported to modulate food intake. However, little is known regarding the underlying mechanisms. The stable oligosomatostatin analog, des-AA1,2,4,5,12,13-[DTrp8]-somatostatin (ODT8-SST), like somatostatin, binds to all five somatostatin receptors (sst1–5). We characterized the effects of ODT8-SST injected intracerebroventricularly (icv) on food consumption and related mechanisms of action in freely fed rats. ODT8-SST (0.3 and 1 μg per rat, icv) injected during the light or dark phase induced an early onset (within 1 h) and long-lasting (4 h) increase in food intake in nonfasted rats. By contrast, ip injection (0.3–3 mg/kg) or icv injection of selective sst1 or sst4 agonists (1 μg per rat) had no effect. The 2 h food intake response during the light phase was blocked by icv injection of a sst2 antagonist, the neuropeptide Y (NPY) Y1 receptor antagonist, BIBP-3226, and ip injection of the μ-opioid receptor antagonist, naloxone, and not associated with changes in plasma ghrelin levels. ODT8-SST (1 μg per rat, icv) stimulated gastric emptying of a solid meal which was also blocked by naloxone. The increased food intake was accompanied by a sustained increase in respiratory quotient, energy expenditure, and drinking as well as μ-opioid receptor-independent grooming behavior and hyperthermia, while ambulatory movements were not altered after ODT8-SST (1 μg per rat, icv). These data show that ODT8-SST acts primarily through brain sst2 receptors to induce a long-lasting orexigenic effect that involves the activation of Y1 and opiate-receptors, accompanied by enhanced gastric transit and energy expenditure suggesting a modulation of NPYergic and opioidergic orexigenic systems by brain sst2 receptors.

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Neuromedin U has a physiological role in the regulation of food intake and partially mediates the effects of leptin

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00404.2004 ◽

2005 ◽

Vol 289 (2) ◽

pp. E301-E305 ◽

Cited By ~ 20

Author(s):

Preeti H. Jethwa ◽

Caroline J. Small ◽

Kirsty L. Smith ◽

Asha Seth ◽

Sarah J. Darch ◽

...

Keyword(s):

Adipose Tissue ◽

Food Intake ◽

Energy Expenditure ◽

Immunoglobulin G ◽

Intraperitoneal Administration ◽

Physiological Role ◽

Dark Phase ◽

Fasted Rats

Intracerebroventricular (ICV) administration of Neuromedin U (NMU), a hypothalamic neuropeptide, or leptin, an adipostat hormone released from adipose tissue, reduces food intake and increases energy expenditure. Leptin stimulates the release of NMU in vitro, and NMU expression is reduced in models of low or absent leptin. We investigated the role of NMU in mediating leptin-induced satiety. ICV administration of anti-NMU immunoglobulin G (IgG) (5 nmol) to satiated rats significantly increased food intake 4 h after injection, an effect seen for ≤8 h after injection. ICV administration of NMU (1 nmol) to fasted rats reduced food intake 1 h after injection compared with control, an effect attenuated by pretreatment with anti-NMU IgG. ICV administration of leptin (0.625 nmol) reduced 24-h food intake. This was partially attenuated by the administration of anti-NMU IgG [24 h after onset of dark phase: vehicle, 22.5 ± 2.0 g; leptin, 13.7 ± 2.3 g ( P < 0.005 vs. vehicle), leptin/NMU IgG, 19.4 ± 1.3 g ( P < 0.05 vs. leptin)]. Intraperitoneal administration of leptin (1.1 mg/kg body wt) reduced 24-h food intake. This was partially attenuated by ICV administration of anti-NMU IgG [24 h after onset of dark phase: vehicle, 31.4 ± 4.9 g; leptin, 20.8 ± 2.6 g ( P < 0.01 vs. vehicle); leptin/NMU IgG, 28.7 ± 1.1 g ( P < 0.01 vs. leptin)]. These results suggest that NMU plays a physiological role in the regulation of appetite and partially mediates the leptin-induced satiety.

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Metabolic Changes Induced by the Biliopancreatic Diversion in Diet-Induced Obesity in Male Rats: The Contributions of Sleeve Gastrectomy and Duodenal Switch

Endocrinology ◽

10.1210/en.2014-1785 ◽

2015 ◽

Vol 156 (4) ◽

pp. 1316-1329 ◽

Cited By ~ 17

Author(s):

Elena-Dana Baraboi ◽

Wei Li ◽

Sébastien M. Labbé ◽

Marie-Claude Roy ◽

Pierre Samson ◽

...

Keyword(s):

Body Weight ◽

Sleeve Gastrectomy ◽

Energy Expenditure ◽

Biliopancreatic Diversion ◽

Duodenal Switch ◽

The Body ◽

Male Rats ◽

Dark Phase ◽

Interscapular Brown Adipose Tissue ◽

Brown Adipose

Abstract The mechanisms underlying the body weight and fat loss after the biliopancreatic diversion with duodenal switch (BPD/DS) remain to be fully delineated. The aim of this study was to examine the contributions of the two main components of BPD/DS, namely sleeve gastrectomy (SG) and duodenal switch (DS), on energy balance changes in rats rendered obese with a high-fat (HF) diet. Three different bariatric procedures (BPD/DS, SG, and DS) and three sham surgeries were performed in male Wistar rats. Sham-operated animals fed HF were either fed ad libitum (Sham HF) or pair weighed (Sham HF PW) by food restriction to the BPD/DS rats. A group of sham-operated rats was kept on standard chow and served as normal diet control (Sham Chow). All three bariatric surgeries resulted in a transient reduction in food intake. SG per se induced a delay in body weight gain. BPD/DS and DS led to a noticeable gut malabsorption and a reduction in body weight and fat gains along with significant elevations in plasma levels of glucagon-like peptide-17–36 and peptide YY. BPD/DS and DS elevated energy expenditure above that of Sham HF PW during the dark phase. However, they reduced the volume, oxidative metabolism, and expression of thermogenic genes in interscapular brown adipose tissue. Altogether the results of this study suggest that the DS component of the BPD/DS, which led to a reduction in digestible energy intake while sustaining energy expenditure, plays a key role in the improvement in the metabolic profile led by BPD/DS in rats fed a HF diet.

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Reduced Energy Expenditure and Increased Inflammation Are Early Events in the Development of Ovariectomy-Induced Obesity

Endocrinology ◽

10.1210/en.2008-1405 ◽

2009 ◽

Vol 150 (5) ◽

pp. 2161-2168 ◽

Cited By ~ 240

Author(s):

Nicole H. Rogers ◽

James W. Perfield ◽

Katherine J. Strissel ◽

Martin S. Obin ◽

Andrew S. Greenberg

Keyword(s):

Gene Expression ◽

Adipose Tissue ◽

Food Intake ◽

Energy Expenditure ◽

Hepatic Steatosis ◽

Ovarian Function ◽

Dark Phase ◽

Adipose Tissue Inflammation ◽

Tissue Inflammation ◽

Age Related

Menopause, an age-related loss of ovarian hormone production, promotes increased adiposity and insulin resistance. However, the diet-independent mechanism by which loss of ovarian function promotes increased adipose tissue mass and associated metabolic pathologies remains unclear. To address this question, we monitored food intake and weight gain of ovariectomized (OVX) mice and sham OVX (SHM) mice for 12 wk. Although food intake was similar, OVX mice gained 25% more weight than SHM mice. Moreover, the OVX mice accumulated 4.7- and 4.4-fold more perigonadal and inguinal adipose tissue by weight, respectively, with 4.4-fold (perigonadal, P < 0.001) and 5.3-fold (inguinal, P < 0.01) larger adipocytes and no change in adipocyte cell number. OVX-induced adiposity was coincident with an 18% decrease in metabolic rate during the dark phase (P = 0.001) as well as an 11% decrease during the light phase (P = 0.03). In addition, ambulatory activity levels of OVX mice were decreased only during the dark phase (40%, P = 0.008). OVX mice displayed evidence of immune infiltration and inflammation in adipose tissue, because perigonadal and inguinal adipose depots from OVX mice had increased expression of TNFα, iNOS, CD11c, and other hallmarks of adipose tissue inflammation. In contrast, expression of the T cell marker CD3 (3.5-fold, P = 0.03) and Th1 cytokine interferon-γ (IFNγ) (2.6-fold, P = 0.02) were elevated in perigonadal but not sc fat. Finally, histology revealed OVX-specific liver hepatic steatosis, coincident with increased PPARγ gene expression and downstream lipogenic gene expression. In summary, OVX in mice decreases energy expenditure, without altering energy intake, resulting in adipocyte hypertrophy, adipose tissue inflammation, and hepatic steatosis.

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