Appetite Genes Research Articles

Betaine improves appetite regulation and glucose-lipid metabolism in mandarin fish (Siniperca chuatsi) fed a high-carbohydrate-diet by regulating the AMPK/mTOR signaling

Diets with high carbohydrate (HC) was reported to have influence on appetite and intermediary metabolism in fish. To illustrate whether betaine could improve appetite and glucose-lipid metabolism in aquatic animals, mandarin fish (Siniperca chuatsi) were fed with the HC diets with or without betaine for 8 weeks. The results suggested that betaine enhanced feed intake by regulating the hypothalamic appetite genes. The HC diet-induced downregulation of AMPK and appetite genes was also positively correlated with the decreased autophagy genes, suggesting a possible mechanism that AMPK/mTOR signaling might regulate appetite through autophagy. The HC diet remarkably elevated transcriptional levels of genes related to lipogenesis, while betaine alleviated the HC-induced hepatic lipid deposition. Additionally, betaine supplementation tended to store the energy storage as hepatic glycogen. Our findings proposed the possible mechanism for appetite regulation through autophagy via AMPK/mTOR, and demonstrated the feasibility of betaine as an aquafeed additive to regulate appetite and intermediary metabolism in fish.

Knockout of lws1 in zebrafish (Danio rerio) reveals its role in regulating feeding and vision-guided behavior.

Long-wave sensitive (LWS) is a G protein-coupled receptor expressed in the retina, and zebrafish is a better model organism for studying vision, but the role of LWS1 in vision-guided behavior of larvae fish has rarely been reported. In this study, we found that zebrafish lws1 and lws2 are tandemly replicated genes, both with six exons, with lws1 being more evolutionarily conserved. The presence of Y277F in the amino acid sequence of lws2 may have contributed to the shift of λmax to green light. We established a lws1 knockout zebrafish model using CRISPR/Cas9 technology. Lws1-/- larvae showed significantly higher levels of feeding and appetite gene (agrp) expression than WT, and significantly lower levels of anorexia gene (pomc, cart) expression. In addition, green light gene compensation was observed in lws1-/- larvae with significantly increased expression levels of rh2-1. The light-dark movement test showed that lws1-/- larvae were more active under light-dark transitions or vibrational stimuli, and the expression of phototransduction-related genes was significantly up-regulated. This study reveals the important role of lws1 gene in the regulation of vision-guided behavior in larvae.

Role of short-wave-sensitive 1 (sws1) in cone development and first feeding in larval zebrafish.

Color vision is mediated by the expression of different major visual pigment proteins (opsins) on retinal photoreceptors. Vertebrates have four classes of cone opsins that are most sensitive to different wavelengths of light: short wavelength sensitive 1 (SWS1), short wavelength sensitive 2 (SWS2), medium wavelength sensitive (RH2), and long wavelength sensitive (LWS). UV wavelengths play important roles in foraging and communication. However, direct evidence provide links between sws1 and first feeding is lacking. Here, CRISPR/Cas9 technology was performed to generate mutant zebrafish lines with sws1 deletion. sws1 mutant zebrafish larvae exhibited decreased sws1, rh2-2, and lws1 expression, and increased rod gene (rho and gnat1) expression. Furthermore, the sws1-deficient larvae exhibited significantly reduced food intake, and the orexigenic genes npy and agrp signaling were upregulated at 6days postfertilization (dpf). The transcription expression of sws1 and rh2-3 genes decreased in sws1-/- adults compared to wild type. Surprisingly, the results of feeding at the adult stage were not the same with larvae. sws1 deficiency did not affect food intake and appetite gene expression at adult stages. These results reveal a role for sws1 in normal cone development and first feeding in larval zebrafish.

Effects of different acute stressors on the regulation of appetite genes in the carp (Cyprinus carpio L.) brain.

Our understanding of the timing of stress responses and specific roles of different regulatory pathways that drive stress responses is incomplete. In particular, the regulation of appetite genes as a consequence of exposure to different stressors has not been studied in sufficient detail in fish. Therefore, a stress trial was conducted with koi carp, aiming at identifying typical effects of stress on regulation of appetite genes. The stressors tank manipulation, air exposure and feed rewarding were chosen. The responses to these stressors were evaluated 10, 30 and 60 min after the stressors were applied. Orexigenic and anorexigenic genes were investigated in four different brain regions (telencephalon, hypothalamus, optic tectum and rhombencephalon). The results show that, apart from the typical appetite regulation in the hypothalamus, the different brain regions also display pronounced responses of appetite genes to the different stressors. In addition, several genes in the serotonergic, dopaminergic and gaba-related pathways were investigated. These genes revealed that rearing in pairs of two and opening of the tank lid affected anorexigenic genes, such as cart and cck, which were not changed by air exposure or feed rewarding. Moreover, distress and eustress led to limited, but distinguishable gene expression pattern changes in the investigated brain regions.

Effects of Different Marine-Based Lipid Sources on Growth Performance, Activities of Digestive Enzyme, Antioxidant Responses, and Lipid Metabolism of Large Yellow Croaker (Larimichthys crocea) Larvae

The study of lipid nutrition is an important guarantee for the development of high-efficiency artificial microdiet for fish larvae. Existing studies on lipid nutrition of larvae mainly focus on nutrient requirements and metabolism through a single lipid source. However, there are few reports on the effects of different marine-based lipid sources on fish larvae. In this study, a 30-day feeding experiment was conducted to evaluate the effects of different dietary marine-based lipid sources on survival, growth performance, appetite gene expression, activities of digestive enzyme, antioxidant responses, and lipid metabolism of large yellow croaker (Larimichthys crocea) larvae (initial weight 4.71 ± 0.21 mg ). Four isonitrogenous (520 g/kg crude protein) and isolipidic (190 g/kg crude lipid) diets were formulated to contain fish oil (FO), krill oil (KO), squid viscera oil (SVO), and Schizochytrium sp. oil (SSO), respectively. Results showed that larvae fed with the SSO diet had significantly higher survival rate (SR) than those fed with dietary FO and SVO ( P < 0.05 ). However, larvae fed with the SSO diet had significantly lower final body weight (FBW) and specific growth rate (SGR) than those fed with other diets ( P < 0.05 ). Furthermore, larvae fed with the SSO diet had significantly higher percentage of total n-3 long-chain polyunsaturated fatty acids (LC-PUFA) than those fed with other diets, followed by KO and SVO diets ( P < 0.05 ). Larvae fed with the SSO diet had significantly lower mRNA expression of orexigenic genes (npy and ghrelin) and significantly higher mRNA expression of anorexigenic gene (cart) than those fed with dietary FO ( P < 0.05 ). Meanwhile, larvae fed with the SSO diet had significantly higher activity of alkaline phosphatase (AKP) in intestinal segments (IS) and brush border membrane (BBM) than those fed with dietary FO and SVO ( P < 0.05 ). Larvae fed with the SSO diet had significantly higher activity of total antioxidant capacity (T-AOC) than those fed with dietary FO ( P < 0.05 ). The TG content and mRNA expression of lipogenesis genes (srebp-1c, fas, and scd1) were markedly lower in larvae fed with SSO, KO, and SVO diets than in those fed with dietary FO ( P < 0.05 ). Meanwhile, larvae fed with KO and SSO diets had significantly higher mRNA expression of the lipolysis gene (cpt-1) than those fed with other diets ( P < 0.05 ). In conclusion, results of the present study showed that FO can be completely replaced in large yellow croaker larvae feed with KO and SVO without negative effects. Moreover, the complete replacement of FO by SSO can improve survival, activities of digestive enzyme, antioxidant responses, and lipid metabolism, despite inhibiting the appetite and growth of large yellow croaker larvae.

Effects of stocking density on the performance, tibia mineralization, and the expression of hypothalamic appetite genes in broiler chickens

Abstract The current study investigated the effects of stocking density (SD) on the performance, tibia mineralization, and the hypothalamic appetite genes expression in broilers. A total of 2,800 1-d-old male broilers (Cobb 500) were distributed in a completely randomized design to 1 of 5 SD treatments with 8 replicate cages for each treatment. The SD treatments were 12.5, 15.0, 17.5, 20.0, and 22.5 birds/m2, corresponding to 50, 60, 70, 80, and 90 birds per cage (4 m2/cage), respectively. The concentration of tibia phosphorus was determined by the ammonium metavanadate colorimetric method and the mRNA abundance in different tissues was measured by the real-time quantitative PCR method. The data were analyzed by the one-way and/or two-way analysis of variance and polynomial contrasts were used to determine the effect of increasing SD. Feed intake linearly decreased (P < 0.05) with increasing SD during d 1-42 production period. On d 42, body weight and tibia breaking strength were significantly lower in the groups of 17.5, 20.0 and 22.5 birds/m2 than in the groups of 12.5 and 15 birds/m2 (P < 0.01). Concentrations of ash and phosphorus in the tibia of broilers linearly decreased (P < 0.03) with increasing SD on d 42. The SD of 22.5 birds/m2 decreased the mRNA abundance of neuropeptide Y (NPY), NPY-receptor (NPYR) 1, and NPYR2 (P < 0.05), while it increased melanocortin receptor 4 mRNA abundance (P = 0.012) in the hypothalamus of broilers as compared with the SD of 12.5 birds/m2 on d 21 and 42. The mRNA abundance of hypothalamic cocaine and amphetamine-regulated transcript (CART), corticotrophin-releasing factor (CRF), and CRF-receptor 1 (CRFR1) were higher (P < 0.05) in the group of 22.5 birds/m2 than in the group of 12.5 birds/m2 on d 21. We concluded that increasing stocking density beyond 15 birds/m2 (corresponding to the 45 kg/m2 at 42 days of age) suppressed final BW and bone mineralization of broilers raised in multitier cage system. Hypothalamic NPY and CRF signaling might be involved in the anorexigenic effect of HSD.

Arthrospira platensis additive enhances the growth performance and antioxidant response in hybrid yellow catfish (Pelteobagrus fulvidraco♀ × Pelteobagrus vachelli♂)

A 56-day fish feeding trial was conducted to investigate the effects of dietary Arthrospira platensis on the growth performance, body chemical composition, serum biochemical parameters and antioxidant capacity in hybrid yellow catfish (Pelteobagrus fulvidraco♀ ×Pelteobagrus vachelli♂). Three experimental feeds were prepared. The protein concentrations of these three experimental diets were similar; one was a commercial diet (CD). The other two diets were with (AP+) or without (AP−) 1% A. platensis. A total of 270 hybrid yellow catfish were randomly divided into nine cages (three cages per treatment, 30 fish per tank) and fed experimental diets. In order to avoid the influence of different protein sources, the proportion of protein in each feed formulation was kept the same. The results revealed that dietary supplementation of 1% A. platensis significantly increased the food intake and growth performance of hybrid yellow catfish (P < 0.05). The crude lipid whole-body content was significantly decreased (P < 0.05). The activity of trypsin from the intestine of the AP+ group was significantly higher than that of AP− (P < 0.05). The albumin (ALB), high density lipoprotein cholesterol (HDL-C), total cholesterol (TCHO), and total protein (TP) from the plasma of AP+ were significantly higher than those of AP− (P < 0.05), while the plasma total bile acid (TBA) decreased (P < 0.05). Plasma glutathione peroxidase (GSH-Px), catalase (CAT), superoxide dismutase (SOD) and lysozyme (LZM) of AP+ were significantly higher than those of AP− (P < 0.05), while the plasma and hepatic malondialdehyde (MDA) were decreased (P < 0.05). The gene expression levels of akt2, pi3k, ghrelin, and npy of AP+ were significantly higher than those of AP− (P < 0.05). The present results indicated that dietary supplementation of 1% A. platensis could promote the growth performance, reduce the fat content, improve the antioxidant capacity, and promote the expression of appetite genes.

Effects of starvation and refeeding on growth performance, appetite, growth hormone-insulin-like growth factor axis levels and digestive function of Acipenser dabryanus.

The aim of this study was to explore the effects and mechanisms of different starvation treatments on the compensatory growth of Acipenser dabryanus. A total of 120 fish (60·532 (sem 0·284) g) were randomly assigned to four groups (fasting 0, 3, 7 or 14 d and then refed for 14 d). During fasting, middle body weight decreased significantly with prolonged starvation. The whole-body and muscle composition, serum biochemical indexes, visceral indexes and digestive enzyme activities had been effected with varying degrees of changes. The growth hormone (GH) level in serum was significantly increased in 14D; however, insulin-like growth factor-1 (IGF-1) showed the opposite trend. The neuropeptide Y (npy) mRNA level in brain was significantly improved in 7D; peptide YY (pyy) mRNA level in intestine was significantly decreased during fasting. After refeeding, the final body weight, percentage weight gain, specific growth rate, feed intake, feed efficiency and protein efficiency ratio showed no difference between 0D and 3D. The changes of whole-body and muscle composition, serum biochemical indexes, visceral indexes and digestive enzyme activities had taken place in varying degrees. GH levels in 3D and 7D were significantly higher than those in the 0D; the IGF-1 content decreased significantly during refeeding. There was no significant difference in npy and pyy mRNA levels. These results indicated that short-term fasting followed by refeeding resulted in full compensation and the physiological and biochemical effects on A. dabryanus were the lowest after 3 d of starvation and 14 d of refeeding. Additionally, compensation in A. dabryanus may be mediated by appetite genes and GH, and the degree of compensation is also affected by the duration of starvation.

Dietary Allicin Improved the Survival and Growth of Large Yellow Croaker (Larimichthys crocea) Larvae via Promoting Intestinal Development, Alleviating Inflammation and Enhancing Appetite.

A 30-day feeding experiment was conducted to investigate effects of dietary allicin on survival, growth, antioxidant capacity, innate immunity and expression of inflammatory and appetite related genes in large yellow croaker larvae. Four iso-nitrogenous (53% crude protein) and iso-lipidic (19% crude lipid) diets were formulated via supplementing graded levels of allicin (0.0 (the control), 0.005, 0.01, and 0.02% dry diet, respectively). Results showed that, among dietary treatments, larvae fed the diet with 0.005% allicin had the highest survival rate (SR) (P < 0.05), while larvae fed the diet with 0.01% allicin had the highest specific growth rate (SGR) (P < 0.05). Activities of α-amylase in both pancreatic (PS) and intestine segments (IS) of larvae fed the diet with 0.01% allicin were significantly lower than that in the control (P < 0.05). On the other hand, the supplementation of 0.01% allicin in diets significantly increased activities of alkaline phosphatase (AKP) and leucine aminopeptidase (LAP) in the intestinal brush border membrane (BBM) of larvae than the control (P < 0.05), indicating the promoting roles of allicin on fish larval intestinal development. Moreover, compared to the control, both the nitric oxide (NO) content and the activity of nitric oxide synthase (NOS) were significantly up-regulated in larvae fed the diet with 0.005% allicin, and catalase (CAT) were significantly upregulated in larvae fed the diet with 0.02% allicin (P < 0.05). Transcriptional levels of pro-inflammatory genes including cyclooxygenase-2 (cox-2), interleukin-1β (il-1β) and interleukin-6 (il-6) significantly decreased with increasing allicin, compared to the control. The expression of appetite genes including npy, ghrelin and leptin significantly increased with the prolonged fasting period, and dietary allicin supplementation significantly increased the transcriptional level of neuropeptide Y (npy) at 0.01%, while increased the transcriptional level of leptin in larvae at 0.02% dosages (P < 0.05). These results showed that the supplementation of 0.005% – 0.01% allicin in diets could improve the survival and growth of large yellow croaker larvae probably by promoting intestinal development, alleviating inflammation and enhancing appetite.

Different regulation of branched-chain amino acid on food intake by TOR signaling in Chinese perch (Siniperca chuatsi)

The mTOR signaling pathway integrates energy status with hormonal signals to regulate not only protein synthesis and growth, but also food intake and energy balance. However, the involvement of TOR signaling pathway in food intake regulation is not clearly characterized in fish. To investigate whether TOR signaling is integrated with both hypothalamic neuronal activity and peripheral signaling in Chinese perch (Siniperca chuatsi), intracerebroventricular administration of branched-chain amino acid (BCAA: leucine, valine and isoleucine) and the inhibitor of TOR signaling rapamycin were performed to detect the regulation of TOR signaling on food intake. The results showed that only leucine could stimulate the TOR signaling, but valine and isoleucine inhibit the TOR signaling. The three BCAA also showed different effects on the food intake and the expression of appetite control genes (hypothalamic neuronal signaling: npy, agrp, pomc, and peripheral hormone: ghrelin, leptin). The up-regulation or down-regulation of TOR signaling by leucine or valine, might suppress or stimulate the food intake through modulating the protein levels of anorexigenic POMC, respectively. We also found the same effects of leucine, valine or isoleucine on the TOR signaling and appetite gene expression in the primary brain cells of Chinese perch. In addition, the different regulation of BCAA on TOR signaling could be attributed to the regulation of BCAA on the interaction between SESN2 and GATOR. These results indicate that three BCAA exhibit the different regulatory roles on the TOR signaling and food intake in fish, unlike in mammals, BCAA activate mTOR signaling.

Insights into response to food intake in anadromous Coilia nasus through stomach transcriptome analysis

Coilia nasus is a valuable commercial migratory fish species with ecological and economic importance in China. To explore the molecular mechanisms underlying the response to food intake, the stomach transcriptomes of feeding and non-feeding C. nasus were analysed via RNA-seq. A total of 610,640,864 clean reads were obtained, and annotation to six databases identified 63,567 unigenes. Comparative analysis of the gene expression in feeding and non-feeding C. nasus identified 1,968 differentially expressed genes (p < .05), including 1,180 up-regulated and 788 down-regulated genes. Our results showed that stomach distention activated the vagal afferent neurons, resulting in satiation. Several of the most relevant appetite genes (e.g. leptin receptor [LepR], somatostatin [SS], nucleobindin-2 [NUCB2], 5-hydroxytryptamine receptor [5-HTR], growth hormone receptor [GHR]) were also involved in the regulation of food intake and led to the termination of feeding. Furthermore, significant differences were observed in the genes encoding key enzymes involved in metabolism such as the tricarboxylic acid cycle (TCA) pathways, fatty acid synthesis and glycolysis, indicating that C. nasus utilizes food for its energy and nutrient contents to support life and gonadal development. These findings provide valuable insights into the mechanisms underlying appetite and metabolic regulation in anadromous fish and create a foundation for further research on C. nasus artificial breeding and migration energetics.

Sex specific effect of ATPase inhibitory factor 1 on body weight: studies in high fat diet induced obese mice and genetic association studies in humans

BackgroundBased on the metabolic effect of exogenous ATPase inhibitory factor 1 (IF1) on glucose metabolism, we tested whether IF1 treatment is effective in ameliorating weight gain and whether its effects are sex specific. MethodsHFD-fed C57BL/6 mice were treated with IF1 (5 mg/kg body weight, injected intraperitoneally). The underlying mechanisms of effect of IF1 on body weight were investigated in vitro and in vivo. Associations between genotypes of IF1 and obesity and relevant phenotype were further tested at the population level. ResultsChronic treatment with IF1 significantly decreased body weight gain by regulating food intake of HFD-fed male mice. IF1 activated the AKT/mTORC pathway and modulated the expression of appetite genes in the hypothalamus of HFD-fed male mice and its effect was confirmed in hypothalamic cell lines as well as hypothalamic primary cells. This required the interaction of IF1 with β-F1-ATPase on the plasma membrane of hypothalamic cells, which led to an increase in extracellular ATP production. In addition, IF1 treatment showed sympathetic nerve activation as measured by serum norepinephrine levels and UCP-1 expression in the subcutaneous fat of HFD-fed male mice. Notably, administration of recombinant IF1 to HFD-fed ovariectomized female mice showed remarkable reductions in food intake as well as body weight, which was not observed in wild-type 5-week female mice. Lastly, sex-specific genotype associations of IF1 with obesity prevalence and metabolic traits were demonstrated at the population level in humans. IF1 genetic variant (rs3767303) was significantly associated with lower prevalence of obesity and lower levels of body mass index, waist circumference, hemoglobin A1c, and glucose response area only in male participants. ConclusionIF1 is involved in weight regulation by controlling food intake and potentially sympathetic nerve activation in a sex-specific manner.

Appetite regulating genes may contribute to herbivory versus carnivory trophic divergence in haplochromine cichlids.

Feeding is a complex behaviour comprised of satiety control, foraging, ingestion and subsequent digestion. Cichlids from the East African Great Lakes are renowned for their diverse trophic specializations, largely predicated on highly variable jaw morphologies. Thus, most research has focused on dissecting the genetic, morphological and regulatory basis of jaw and teeth development in these species. Here for the first time we explore another aspect of feeding, the regulation of appetite related genes that are expressed in the brain and control satiety in cichlid fishes. Using qPCR analysis, we first validate stably expressed reference genes in the brain of six haplochromine cichlid species at the end of larval development prior to foraging. We next evaluate the expression of 16 appetite related genes in herbivorous and carnivorous species from the parallel radiations of Lake Tanganyika, Malawi and Victoria. Interestingly, we find increased expression of two appetite-regulating genes (anorexigenic genes), cart and npy2r, in the brain of carnivorous species in all the three lakes. This supports the notion that appetite gene regulation might play a part in determining trophic niche specialization in divergent cichlid species, already prior to exposure to different diets. Our study contributes to the limited body of knowledge on the neurological circuitry that controls feeding transitions and adaptations in cichlids and other teleosts.

Maternal Obesity during Pregnancy Alters Daily Activity and Feeding Cycles, and Hypothalamic Clock Gene Expression in Adult Male Mouse Offspring.

An obesogenic diet adversely affects the endogenous mammalian circadian clock, altering daily activity and metabolism, and resulting in obesity. We investigated whether an obese pregnancy can alter the molecular clock in the offspring hypothalamus, resulting in changes to their activity and feeding rhythms. Female mice were fed a control (C, 7% kcal fat) or high fat diet (HF, 45% kcal fat) before mating and throughout pregnancy. Male offspring were fed the C or HF diet postweaning, resulting in four offspring groups: C/C, C/HF, HF/C, and HF/HF. Daily activity and food intake were monitored, and at 15 weeks of age were killed at six time-points over 24 h. The clock genes Clock, Bmal1, Per2, and Cry2 in the suprachiasmatic nucleus (SCN) and appetite genes Npy and Pomc in the arcuate nucleus (ARC) were measured. Daily activity and feeding cycles in the HF/C, C/HF, and HF/HF offspring were altered, with increased feeding bouts and activity during the day and increased food intake but reduced activity at night. Gene expression patterns and levels of Clock, Bmal1, Per2, and Cry2 in the SCN and Npy and Pomc in the ARC were altered in HF diet-exposed offspring. The altered expression of hypothalamic molecular clock components and appetite genes, together with changes in activity and feeding rhythms, could be contributing to offspring obesity.

Identification of hypothalamic genes in associating with food intake during incubation behavior in domestic chicken.

The molecular mechanism underlying in the onset and maintenance of incubation behavior are not fully understood, and it is still unknown the reason why White Leghorn, a layer strain, hens never display incubation behavior. Therefore, to explore specific hypothalamic genes regulating incubation behavior, cap analysis of gene expression (CAGE) were applied to comparison between incubating Silkie and laying White Leghorn hens. In addition, mRNA expression of some differentially expressed genes (DEGs) and melanocortinergic appetite genes including agouti-related peptide (AgRP) and pro-opiomelanocortin (POMC) was also analyzed on Silkie hens under natural anorexia and starvation. The CAGE identified 217 hypothalamic DEGs in incubating Silkie hens, and that of two, transthyretin (TTR) and prolactin-releasing peptide (PrRP), suggested as appetite gene, were markedly up- and down-regulated in incubating hens, respectively. In addition, AgRP and POMC expression also increased in incubating bird. mRNA expression of TTR, PrRP, and appetite genes were not differed significantly by starvation, although TTR mRNA expression was relatively high in fasting hens. Consequently, transcriptome by CAGE identified a number of hypothalamic genes differentially expressed by incubation behavior in Silkie hens. Of these, it is suggested that TTR and PrRP may, at least in part, be related to adaptation to natural anorexia in incubating Silkie chickens.

Chronic heat stress alters hypothalamus integrity, the serum indexes and attenuates expressions of hypothalamic appetite genes in broilers

The hypothalamus is crucial to ensure the functionality of the entire organisms, such as body temperature, feed intake and energy regulation. Exposing broilers to high ambient temperature usually induces lower feed intake and energy imbalance. We investigated the molecular mechanisms by which heat stress impairs the appetite via dysfunction in hypothalamus of the broilers. Broilers were allocated to three groups: the normal control (NC) group, and fed ad libitum; heat-stress (HS) group, and fed ad libitum; pair-fed (PF) group, which received the feed intake equal to HS group. Experiment lasted from the age of 28 to 42 d. The results showed that HS increased the head surface temperature of broiler and changed hypothalamic ultrastructure. HS treatment also increased the serum corticosterone in the broilers after 7 days of heat stress, elevated the FT4 and FT3 after 14 days of heat stress. Heat stress of 14 days showed a tendency to increase the leptin. However, the serum corticosterone in the HS group had no significant difference after 14 days of heat stress. In addition, HS treatment decreased the expression of orexigenic gene neuropeptide Y (NPY) after 14 days of heat stress, while HS treatment had no effect on the reactive oxygen species (ROS), as well as the gene expression of AMPKα1 and LKB1 in the hypothalamus. In conclusion, HS increased the surface temperature of head in broiler, and then altered the integrity of hypothalamus. Meanwhile, HS increased the serum corticosterone which may ascribe to the activation of HPA axis in the broilers. In addition, chronic heat stress decreased the expression of orexigenic gene NPY, which may cause the broiler to reduce feed intake.

Glycaemic Index of Maternal Dietary Carbohydrate Differentially Alters Fto and Lep Expression in Offspring in C57BL/6 Mice.

Maternal diet and gestational hyperglycaemia have implications for offspring health. Leptin (LEP) and fat mass and obesity-associated (FTO) alleles are known to influence body fat mass in humans, potentially via effects on appetite. We hypothesized that expression of Fto, Lep, and other appetite-related genes (Argp, Npy, Pomc, Cart, Lepr) in the offspring of female mice are influenced by the glycaemic index (GI) of carbohydrates in the maternal diet. C57BL/6 mice were randomly assigned to low or high GI diets and mated with chow-fed males at eight weeks of age. Male pups were weaned at four weeks and randomly divided into two groups, one group following their mother’s diet (LL and HH), and one following the standard chow diet (LC and HC) to 20 weeks. Fto expression was 3.8-fold higher in the placenta of mothers fed the high GI diet (p = 0.0001) and 2.5-fold higher in the hypothalamus of 20-week old offspring fed the high GI (HH vs. LL, p < 0.0001). By contrast, leptin gene (Lep) expression in visceral adipose tissue was 4.4-fold higher in four-week old offspring of low GI mothers (LC vs. HC, p < 0.0001) and 3.3-fold higher in visceral adipose tissue of 20-week old animals (LL vs. HH, p < 0.0001). Plasma ghrelin and leptin levels, and hypothalamic appetite genes were also differentially regulated by maternal and offspring diet. These findings provide the first evidence in an animal model that maternal high GI dietary carbohydrates that are digested and absorbed faster may contribute to programming of appetite in offspring.

Melatonin treatment suppresses appetite genes and improves adipose tissue plasticity in diet-induced obese zebrafish.

Overweight and obesity are important risk factors for diabetes, cardiovascular diseases, and premature death in modern society. Recently, numerous natural and synthetic compounds have been tested in diet-induced obese animal models, to counteract obesity. Melatonin is a circadian hormone, produced by pineal gland and extra-pineal sources, involved in processes which have in common a rhythmic expression. In teleost, it can control energy balance by activating or inhibiting appetite-related peptides. The study aims at testing effects of melatonin administration to control-fed and overfed zebrafish, in terms of expression levels of orexigenic (Ghrelin, orexin, NPY) and anorexigenic (leptin, POMC) genes expression and morphometry of visceral and subcutaneous fat depots. Adult male zebrafish (n = 56) were divided into four dietary groups: control, overfed, control + melatonin, overfed + melatonin. The treatment lasted 5 weeks and BMI levels of every fish were measured each week. After this period fishes were sacrificed; morphological and morphometric studies have been carried out on histological sections of adipose tissue and adipocytes. Moreover, whole zebrafish brain and intestine were used for qRT-PCR. Our results demonstrate that melatonin supplementation may have an effect in mobilizing fat stores, in increasing basal metabolism and thus in preventing further excess fat accumulation. Melatonin stimulates the anorexigenic and inhibit the orexigenic signals. It seems that adequate melatonin treatment exerts anti-obesity protective effects, also in a diet-induced obesity zebrafish model, that might be the result of the restoration of many factors: the final endpoint reached is weight loss and stabilization of weight gain.

Placenta and appetite genes GDF15 and IGFBP7 are associated with hyperemesis gravidarum

Hyperemesis gravidarum (HG), severe nausea and vomiting of pregnancy, occurs in 0.3–2% of pregnancies and is associated with maternal and fetal morbidity. The cause of HG remains unknown, but familial aggregation and results of twin studies suggest that understanding the genetic contribution is essential for comprehending the disease etiology. Here, we conduct a genome-wide association study (GWAS) for binary (HG) and ordinal (severity of nausea and vomiting) phenotypes of pregnancy complications. Two loci, chr19p13.11 and chr4q12, are genome-wide significant (p < 5 × 10−8) in both association scans and are replicated in an independent cohort. The genes implicated at these two loci are GDF15 and IGFBP7 respectively, both known to be involved in placentation, appetite, and cachexia. While proving the casual roles of GDF15 and IGFBP7 in nausea and vomiting of pregnancy requires further study, this GWAS provides insights into the genetic risk factors contributing to the disease.

Effects of Maternal and Post-Weaning High-Fat Diet on Leptin Resistance and Hypothalamic Appetite Genes in Sprague Dawley Rat Offspring.

The defective satiation signaling may contribute to the etiology of obesity. We investigated how dietary modification during maternal (pregnancy and lactation) and post-weaning affects obesity, insulin resistance (IR) and hypothalamic appetite responses in offspring in adulthood. Pregnant female SD rats were randomly allocated to either maternal high-fat diet (43% energy from fat) or control diet (12% energy from fat) until the end of suckling. After weaning for additional 4 weeks, half of the offsprings were continuously fed the same diet as the dam (C-C and H-H groups); the remainder received the counterpart diet (C-H and H-C groups). The long-term high-fat diet during maternal and post-weaning period (H-H group) led to susceptibility to obesity and IR through the significant increases of hypothalamic orexigenic genes compared to the maternal and post-weaning control diet group (C-C group). In contrast, the hypothalamic expression levels of anorexigenic genes, apolipoprotein E, leptin receptor, and activated signal transducer and activator of transcription protein 3 were significantly lower in H-H group with elevations in circulating insulin and leptin and body fat mass. However, dietary changes after weaning (H-C and C-H groups) partially modified these conditions. These results suggest that maternal and post-weaning diet conditions can potentially disrupt hypothalamic neuronal signal irrelevantly, which is essential for leptin's regulation of energy homeostasis and induce the risk of offspring to future metabolic disorders.