scholarly journals Genetic architecture drives seasonal onset of hibernation in the 13-lined ground squirrel

2017 ◽  
Author(s):  
Katharine R. Grabek ◽  
Thomas F. Cooke ◽  
L. Elaine Epperson ◽  
Kaitlyn K. Spees ◽  
Gleyce F. Cabral ◽  
...  
Keyword(s):  
Food Intake ◽  
Body Mass ◽  
Genetic Architecture ◽  
Energy Homeostasis ◽  
Muscarinic Acetylcholine Receptor ◽  
Ground Squirrels ◽  
Eqtl Analysis ◽  
A Genome ◽  
Prohormone Convertase 2 ◽  
Genotype By Sequencing

AbstractHibernation is a highly dynamic phenotype whose timing, for many mammals, is controlled by a circannual clock and accompanied by rhythms in body mass and food intake. When housed in an animal facility, 13-lined ground squirrels exhibit individual variation in the seasonal onset of hibernation, which is not explained by environmental or biological factors, such as body mass and sex. We hypothesized that underlying genetic architecture instead drives variation in this timing. After first increasing the contiguity of the genome assembly, we therefore employed a genotype-by-sequencing approach to characterize genetic variation in 153 13-lined ground squirrels. Combining this with datalogger records, we estimated high heritability (61-100%) for the seasonal onset of hibernation. After applying a genome-wide scan with 46,996 variants, we also identified 21 loci significantly associated with hibernation immergence, which alone accounted for 54% of the variance in the phenotype. The most significant marker (SNP 15, p=3.81×10−6) was located near prolactin-releasing hormone receptor (PRLHR), a gene that regulates food intake and energy homeostasis. Other significant loci were located near genes functionally related to hibernation physiology, including muscarinic acetylcholine receptor M2 (CHRM2), involved in the control of heart rate, exocyst complex component 4 (EXOC4) and prohormone convertase 2 (PCSK2), both of which are involved in insulin signaling and processing. Finally, we applied an expression quantitative loci (eQTL) analysis using existing transcriptome datasets, and we identified significant (q<0.1) associations for 9/21 variants. Our results highlight the power of applying a genetic mapping strategy to hibernation and present new insight into the genetics driving its seasonal onset.

scholarly journals Genetic variation drives seasonal onset of hibernation in the 13-lined ground squirrel

2019 ◽  
Vol 2 (1) ◽  
Author(s):  
Katharine R. Grabek ◽  
Thomas F. Cooke ◽  
L. Elaine Epperson ◽  
Kaitlyn K. Spees ◽  
Gleyce F. Cabral ◽  
...  
Keyword(s):  
Genetic Variation ◽  
Causal Variant ◽  
Ground Squirrels ◽  
Genome Wide ◽  
A Genome ◽  
Gene Associations ◽  
Significant Locus ◽  
High Heritability ◽  
Genotype By Sequencing ◽  
Whole Genome Resequencing

AbstractHibernation in sciurid rodents is a dynamic phenotype timed by a circannual clock. When housed in an animal facility, 13-lined ground squirrels exhibit variation in seasonal onset of hibernation, which is not explained by environmental or biological factors. We hypothesized that genetic factors instead drive variation in timing. After increasing genome contiguity, here, we employ a genotype-by-sequencing approach to characterize genetic variation in 153 ground squirrels. Combined with datalogger records (n = 72), we estimate high heritability (61–100%) for hibernation onset. Applying a genome-wide scan with 46,996 variants, we identify 2 loci significantly (p < 7.14 × 10−6), and 12 loci suggestively (p < 2.13 × 10−4), associated with onset. At the most significant locus, whole-genome resequencing reveals a putative causal variant in the promoter of FAM204A. Expression quantitative trait loci (eQTL) analyses further reveal gene associations for 8/14 loci. Our results highlight the power of applying genetic mapping to hibernation and present new insight into genetics driving its onset.

Increased heat loss affects hibernation in golden-mantled ground squirrels

2004 ◽  
Vol 287 (1) ◽  
pp. R167-R173 ◽  
Author(s):  
Alexander S. Kauffman ◽  
Matthew J. Paul ◽  
Irving Zucker
Keyword(s):  
Food Intake ◽  
Heat Loss ◽  
Body Mass ◽  
Complete Removal ◽  
Ground Squirrels ◽  
Control Procedure ◽  
Ambient Temperatures ◽  
Spermophilus Lateralis ◽  
Maintain Body Temperature ◽  
Body Heat

During hibernation at ambient temperatures (Ta) above 0°C, rodents typically maintain body temperature (Tb) ∼1°C above Ta, reduce metabolic rate, and suspend or substantially reduce many physiological functions. We tested the extent to which the presence of an insulative pelage affects hibernation. Tb was recorded telemetrically in golden-mantled ground squirrels ( Spermophilus lateralis) housed at a Ta of 5°C; food intake and body mass were measured at regular intervals throughout the hibernation season and after the terminal arousal. Animals were subjected to complete removal of the dorsal fur or a control procedure after they had been in hibernation for 3–4 wk. Shaved squirrels continued to hibernate with little or no change in minimum Tb, bout duration, duration of periodic normothermic bouts, and food intake during normothermia. Rates of rewarming from torpor were, however, significantly slower in shaved squirrels, and rates of body mass loss were significantly higher, indicating increased depletion of white adipose energy stores. An insulative pelage evidently conserves energy over the course of the hibernation season by decreasing body heat loss and reducing energy expenditure during periodic arousals from torpor and subsequent intervals of normothermia. This prolongs the hibernation season by several weeks, thereby eliminating the debilitating consequences associated with premature emergence from hibernation.

scholarly journals Differential effects of glucocorticoids on energy homeostasis in Syrian hamsters

2011 ◽  
Vol 301 (2) ◽  
pp. E307-E316 ◽  
Author(s):  
Matia B. Solomon ◽  
Randall R. Sakai ◽  
Stephen C. Woods ◽  
Michelle T. Foster
Keyword(s):  
Food Intake ◽  
Body Mass ◽  
Energy Homeostasis ◽  
Fat Tissue ◽  
Thymic Involution ◽  
Syrian Hamsters ◽  
Differential Effects ◽  
Body Adiposity ◽  
Increase Food Intake ◽  
Response To Stress

Syrian hamsters, like many humans, increase food intake and body adiposity in response to stress. We hypothesized that glucocorticoids (cortisol and corticosterone) mediate these stress-induced effects on energy homeostasis. Because Syrian hamsters are dual secretors of cortisol and corticosterone, differential effects of each glucocorticoid on energy homeostasis were investigated. First, adrenal intact hamsters were injected with varying physiological concentrations of cortisol, corticosterone, or vehicle to emulate our previously published defeat regimens (i.e., 1 injection/day for 5 days). Neither food intake nor body weight was altered following glucocorticoid injections. Therefore, we investigated the effect of sustained glucocorticoid exposure on energy homeostasis. This was accomplished by implanting hamsters with supraphysiological steady-state pellets of cortisol, corticosterone, or cholesterol as a control. Cortisol, but not corticosterone, significantly decreased food intake, body mass, and lean and fat tissue compared with controls. Despite decreases in body mass and adiposity, cortisol significantly increased circulating free fatty acids, triglyceride, cholesterol, and hepatic triglyceride concentrations. Although corticosterone did not induce alterations in any of the aforementioned metabolic end points, Syrian hamsters were responsive to the effects of corticosterone since glucocorticoids both induced thymic involution and decreased adrenal mass. These findings indicate that cortisol is the more potent glucocorticoid in energy homeostasis in Syrian hamsters. However, the data suggest that cortisol alone does not mediate stress-induced increases in food intake or body mass in this species.

scholarly journals Deficiency of Irx5 protects mice from diet-induced obesity and associated metabolic abnormalities

2021 ◽  
Author(s):  
Joe Son ◽  
Kyoung-Han Kim ◽  
Chi-chung Hui
Keyword(s):  
Food Intake ◽  
Body Mass ◽  
Energy Homeostasis ◽  
Caloric Intake ◽  
Mass Composition ◽  
Metabolic Abnormalities ◽  
Diet Induced Obesity ◽  
Body Mass Composition ◽  
Polygenic Obesity

Obesity, a leading cause of several metabolic abnormalities, is mainly due to an imbalance of energy homeostasis. IRX3 and IRX5 have been suggested as determinants of obesity in connection with the intronic variants of FTO, the strongest genetic risk factor of polygenic obesity in humans. Although the causal effects of Irx3 on obesity and its related metabolic consequences have been demonstrated in vivo, the metabolic function of Irx5 remains unclear. In this study, using mice homozygous for an Irx5-knockout (Irx5KO) allele, we show a direct link between Irx5 expression and regulation of body mass/composition and energy homeostasis. Irx5KO mice are leaner and resistant to diet-induced obesity and associated metabolic abnormalities, primarily through the loss of adiposity with an increase in basal metabolic rate with adipose thermogenesis and lower food intake. Furthermore, our long-term feeding analysis found that Irx3 mutant mouse lines also have less food intake, indicating that lower caloric intake also contributes to their lean phenotype. Together, these results demonstrate that Irx5 is critical for energy homeostasis and regulation of body mass/composition and suggest that it likely acts in other tissues beyond adipocytes.

Central Histamine, the H3-Receptor and Obesity Therapy

2019 ◽  
Vol 18 (7) ◽  
pp. 516-522
Author(s):  
Néstor F. Díaz ◽  
Héctor Flores-Herrera ◽  
Guadalupe García-López ◽  
Anayansi Molina-Hernández
Keyword(s):  
Body Weight ◽  
Food Intake ◽  
Animal Studies ◽  
Energy Homeostasis ◽  
Receptor Activation ◽  
Receptor Ligands ◽  
Histaminergic System ◽  
H3 Receptor ◽  
Weight One ◽  
The Central Nervous System

The brain histaminergic system plays a pivotal role in energy homeostasis, through H1- receptor activation, it increases the hypothalamic release of histamine that decreases food intake and reduces body weight. One way to increase the release of hypothalamic histamine is through the use of antagonist/inverse agonist for the H3-receptor. Histamine H3-receptors are auto-receptors and heteroreceptors located on the presynaptic membranes and cell soma of neurons, where they negatively regulate the synthesis and release of histamine and other neurotransmitters in the central nervous system. Although several compounds acting as H3-receptor antagonist/inverse agonists have been developed, conflicting results have been reported and only one has been tested as anti-obesity in humans. Animal studies revealed the opposite effect in food intake, energy expeditor, and body weight, depending on the drug, spice, and route of administration, among others. The present review will explore the state of art on the effects of H3-receptor ligands on appetite and body-weight, going through the following: a brief overview of the circuit involved in the control of food intake and energy homeostasis, the participation of the histaminergic system in food intake and body weight, and the H3-receptor as a potential therapeutic target for obesity.

scholarly journals A Genome-Wide Association Study for Hypertensive Kidney Disease in Korean Men

Genes ◽  
2021 ◽  
Vol 12 (5) ◽  
pp. 751
Author(s):  
Hye-Rim Kim ◽  
Hyun-Seok Jin ◽  
Yong-Bin Eom
Keyword(s):  
Blood Pressure ◽  
Kidney Disease ◽  
Association Study ◽  
Genome Wide Association Study ◽  
Genome Wide Association ◽  
Integrated Analysis ◽  
Eqtl Analysis ◽  
Strong Linkage Disequilibrium ◽  
Genome Wide ◽  
A Genome

Hypertension is one of the major risk factors for chronic kidney disease (CKD), and the coexistence of hypertension and CKD increases morbidity and mortality. Although many genetic factors have been identified separately for hypertension and kidney disease, studies specifically focused on hypertensive kidney disease (HKD) have been rare. Therefore, this study aimed to identify loci or genes associated with HKD. A genome-wide association study (GWAS) was conducted using two Korean cohorts, the Health Examinee (HEXA) and Korean Association REsource (KARE). Consequently, 19 single nucleotide polymorphisms (SNPs) were found to be significantly associated with HKD in the discovery and replication phases (p < 5 × 10−8, p < 0.05, respectively). We further analyzed HKD-related traits such as the estimated glomerular filtration rate (eGFR), creatinine, blood urea nitrogen (BUN), systolic blood pressure (SBP) and diastolic blood pressure (DBP) at the 14q21.2 locus, which showed a strong linkage disequilibrium (LD). Expression quantitative trait loci (eQTL) analysis was also performed to determine whether HKD-related SNPs affect gene expression changes in glomerular and arterial tissues. The results suggested that the FANCM gene may affect the development of HKD through an integrated analysis of eQTL and GWAS and was the most significantly associated candidate gene. Taken together, this study indicated that the FANCM gene is involved in the pathogenesis of HKD. Additionally, our results will be useful in prioritizing other genes for further experiments.

scholarly journals Genome-Wide Association Study (GWAS) for Examining the Genomics Controlling Prickle Production in Red Raspberry (Rubus idaeus L.)

Agronomy ◽  
2020 ◽  
Vol 11 (1) ◽  
pp. 27
Author(s):  
Archana Khadgi ◽  
Courtney A. Weber
Keyword(s):  
Association Study ◽  
Genome Wide Association Study ◽  
Genomic Region ◽  
Rubus Idaeus ◽  
Genome Wide Association ◽  
Nucleotide Polymorphisms ◽  
Red Raspberry ◽  
Genome Wide ◽  
A Genome ◽  
Genotype By Sequencing

Red raspberry (Rubus idaeus L.) is an expanding high-value berry crop worldwide. The presence of prickles, outgrowths of epidermal tissues lacking vasculature, on the canes, petioles, and undersides of leaves complicates both field management and harvest. The utilization of cultivars with fewer prickles or prickle-free canes simplifies production. A previously generated population segregating for prickles utilizing the s locus between the prickle-free cultivar Joan J (ss) and the prickled cultivar Caroline (Ss) was analyzed to identify the genomic region associated with prickle development in red raspberry. Genotype by sequencing (GBS) was combined with a genome-wide association study (GWAS) using fixed and random model circulating probability unification (FarmCPU) to analyze 8474 single nucleotide polymorphisms (SNPs) and identify significant markers associated with the prickle-free trait. A total of four SNPs were identified on chromosome 4 that were associated with the phenotype and were located near or in annotated genes. This study demonstrates how association genetics can be used to decipher the genetic control of important horticultural traits in Rubus, and provides valuable information about the genomic region and potential genes underlying the prickle-free trait.

Effects of neurosecretory protein GL on food intake and fat accumulation under different dietary nutrient compositions in rats

2021 ◽  
Author(s):  
Keisuke Fukumura ◽  
Kenshiro Shikano ◽  
Yuaki Narimatsu ◽  
Eiko Iwakoshi-Ukena ◽  
Megumi Furumitsu ◽  
...  
Keyword(s):  
Food Intake ◽  
Feeding Behavior ◽  
Body Mass ◽  
Mass Gain ◽  
Chow Diet ◽  
Tissue Mass ◽  
Fat Accumulation ◽  
Intracerebroventricular Infusion ◽  
Body Mass Gain ◽  
Sucrose Diet

Abstract We recently identified a novel hypothalamic small protein, named neurosecretory protein GL (NPGL), which is involved in energy homeostasis in birds and mammals. However, whether the action of NPGL is influenced by nutritional composition remains unknown. Thus, we investigated the effect of chronic intracerebroventricular infusion of NPGL for 13 days on feeding behavior and body mass gain under a normal chow diet (NC), high-fat diet, high-sucrose diet (HSD), and medium-fat/medium-sucrose diet (MFSD) in rats. NPGL stimulated food intake of NC and MFSD, especially during the light period. By contrast, NPGL decreased body mass gain under NC and increased total white adipose tissue mass in HSD- and MFSD-fed rats. These data suggest that the effects of NPGL on feeding behavior, body mass gain, and fat accumulation depend on nutrient type. Among them, sucrose in diets seems to contribute to fat accumulation elicited by NPGL.

scholarly journals Neonatal nutritional programming impairs adiponectin effects on energy homeostasis in adult life of male rats

2018 ◽  
Vol 315 (1) ◽  
pp. E29-E37 ◽  
Author(s):  
Mariana Peduti Halah ◽  
Paula Beatriz Marangon ◽  
Jose Antunes-Rodrigues ◽  
Lucila L. K. Elias
Keyword(s):  
Body Weight ◽  
Adipose Tissue ◽  
Weight Gain ◽  
Food Intake ◽  
White Adipose Tissue ◽  
Energy Homeostasis ◽  
Body Weight Gain ◽  
Adult Life ◽  
Male Rats ◽  
Nutritional Programming

Neonatal nutritional changes induce long-lasting effects on energy homeostasis. Adiponectin influences food intake and body weight. The aim of this study was to investigate the effects of neonatal nutritional programming on the central stimulation of adiponectin. Male Wistar rats were divided on postnatal (PN) day 3 in litters of 3 (small litter, SL), 10 (normal litter, NL), or 16 pups/dam (large litter, LL). We assessed body weight gain for 60 days, adiponectin concentration, and white adipose tissue weight. We examined the response of SL, NL, and LL rats on body weight gain, food intake, oxygen consumption (V̇o2), respiratory exchange ratio (RER), calorimetry, locomotor activity, phosphorylated-AMP-activated protein kinase (AMPK) expression in the hypothalamus, and uncoupling protein (UCP)-1 in the brown adipose tissue after central stimulus with adiponectin. After weaning, SL rats maintained higher body weight gain despite similar food intake compared with NL rats. LL rats showed lower body weight at weaning, with a catch up afterward and higher food intake. Both LL and SL groups had decreased plasma concentrations of adiponectin at PN60. SL rats had increased white adipose tissue. Central injection of adiponectin decreased body weight and food intake and increased V̇o2, RER, calorimetry, p-AMPK and UCP- 1 expression in NL rats, but it had no effect on SL and LL rats, compared with the respective vehicle groups. In conclusion, neonatal under- and overfeeding induced an increase in body weight gain in juvenile and early adult life. Unresponsiveness to central effects of adiponectin contributes to the imbalance of the energy homeostasis in adult life induced by neonatal nutritional programming.

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