腺苷一磷酸激活蛋白激酶与采食量调节

<正>腺苷一磷酸激活蛋白激酶(AMPK)的概念首次出现在1988年。近几年的研究表明,AMPK在调节细胞能量代谢上起着重要作用,被称作细胞内的“燃料开关”,在动物抵御和适应环境应激的过程中也起着重要作用。最新研究显示,AMPK通过一些激素和养分等途径参与采食量的调节。本文总结了AMPK在采食量调节中的作用和可能机制,揭示研究其与动物营养代谢的重要性关系。     

Central regulation of food intake in the neonatal chick

Regulating food intake is complicated in animals including domestic birds. Just after hatching, neonatal chicks find their food by themselves and they can control food intake, since domestic chicken belongs to the precocial type of avian species. Thus, domestic chickens have relatively well-developed mechanisms of food-intake control at hatching. While many aspects of food-intake regulation in chickens appear similar to that in mammals, there are some responses that are unique to chickens. For instance, some neurotransmitters such as neuropeptide Y (NPY), orexin-A, orexin-B, motilin, melanin-concentrating hormone (MCH), galanin, growth hormone releasing factor (GRF) and ghrelin stimulate feeding in mammals. Only NPY strongly stimulates food intake in birds similar to that observed in mammals; however, both orexins, motilin, MCH and galanin failed to alter food intake of the chick. Moreover, GRF and ghrelin suppressed feeding of chicks. On the other hand, cholecystokinin (CCK), gastrin, glucagon-like peptide-1 (GLP-1), corticotropin-releasing factor (CRF), histamine, α-melanocyte stimulating hormone (α-MSH), leptin and bombesin are known to suppress feeding in mammals. These responses are similar to those of mammals except for leptin. Therefore, the inhibitory mechanisms for feeding are well conserved in chicks.     

Immune and endocrine regulation of food intake in sick animals

To understand why sick animals do not eat, investigators have studied how the immune system interacts with the central nervous system (CNS), where motivation to eat is ultimately controlled. The focus has been on the cytokines secreted by activated mononuclear myeloid cells, which include interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α). Either central or peripheral injection of recombinant IL-1β, IL-6, and TNF-α reduce food-motivated behavior and food intake in rodents. Moreover, these cytokines and their receptors are present in the endocrine system and brain, and antagonism of this system (i.e., the cytokine network) has been shown to block or abrogate anorexia induced by inflammatory stimuli. Recent studies indicate that the same cytokines act on adipocytes and induce secretion of leptin, a protein whose activity has been neuroanatomically mapped to brain areas involved in regulating food intake and energy expenditure. Therefore, many findings converge to suggest that the reduction of food intake in sick animals is mediated by inflammatory cytokines, which convey a message from the immune system to the endocrine system and CNS. The nature of this interaction is the focus of this short review.     

Histochemical localization of inhibin and activin alpha, beta A and beta B subunits in rat gonads.

The localization of alpha, beta A and beta B subunits of inhibin/activin polypeptides was studied in the ovary and testis of sexually mature, immature, and embryonic rats. Specific staining with these three subunits was also evident in the oocytes from embryonic to mature female rats. This result suggests that inhibin- and activin-like substances may be produced in the oocytes and these substances may play a role in the oocyte growth and differentiation. Judging from the intensity of immunoreaction in mature female rats, the three subunits should be produced more abundantly in luteal cells than in the granulosa cells. Immunoreactive alpha, beta A and beta B subunits were observed in the cummulus oophorous in the morning (11:00), but not in the evening (23:00) on proestrus. The results are in well agreement with the previous report that inhibin alpha and beta A subunit mRNA signals decline on proestrus evening. It is supposed that the cyclic change may be related with physiological phenomena prior to the ovulation, such as primary gonadotropin surges, loss of cummulus-oocyte gap junctions, or germinal vesicle breakdown. In both germ cells and Sertoli cells of the testis, alpha, beta A and beta B subunits were more abundant in the embryonic rat than in the mature rat. Although clear reactions with beta A and beta B subunits were detected in Leydig cells, alpha subunit was not detectable in the cells throughout the developmental stages examined.     

Involvement of histaminergic and noradrenergic receptors in the oxytocin-induced food intake in neonatal meat-type chicks

Oxytocin neurons have a physiological role in food intake and energy balance. Several studies have shown that central histaminergic and adrenergic systems synapse on oxytocin neurons but there is no information for their interaction on food intake regulation in birds. The purpose of this study was to examine the effects of intracerebroventricular (ICV) injection of α-fluoromethylhistidine (α-FMH, histidine decarboxylase inhibitor), chlorpheniramine (histamine H1 receptors antagonist), famotidine (histamine H2 receptors antagonist), thioperamide (histamine H3 receptors antagonist), prazosin (α1 receptor antagonist), yohimbine (α2 receptor antagonist), metoprolol (β1 adrenergic receptor antagonist), ICI 118,551 (β2 adrenergic receptor antagonist) and SR59230R (β3 adrenergic receptor antagonist) on oxytocin-induced hypophagia in 3-h food-deprived (FD₃) neonatal broiler chicken. In Experiment 1, 3 h-fasted chicks were given an ICV injection of saline, α-FMH (250 nmol), oxytocin (10 μg) and co-injection of α-FMH + oxytocin. Experiments 2–9 were similar to experiment 1 except birds were injected with chlorpheniramine (300 nmol), famotidine (82 nmol), thioperamide (300 nmol), prazosin (10 nmol), yohimbine (13 nmol), metoprolol (24 nmol), ICI 118,551(5 nmol) and SR59230R (20 nmol) instead of α-FMH, respectively. After injection cumulative food intake was measured until 120 min post injection. According to the results, ICV injection of oxytocin significantly decreased food intake in broiler chickens (P < 0.001). ICV injection of α-FMH significantly attenuated hypophagic effect of oxytocin (P < 0.001). Also, co-injection of chlorpheniramine plus oxytocin significantly decreased the effect of oxytocin on food intake (P < 0.001). Co-administration of thioperamide and oxytocin significantly amplified hypophagic effect of oxytocin in chickens (P < 0.001). In addition, ICI 118,551 attenuated hypophagic effect of oxytocin (P < 0.001); while famotidine, prazosin, yohimbine, metoprolol and SR59230R had no effect on oxytocin- induced food intake in FD3 broiler chickens. These results suggest that the effect of oxytocin on food intake is probably mediated by histaminergic (via H1 and H3 receptors) and noradrenergic (via β2 receptors) systems in broiler chickens.     

Expression of inhibin/activin subunits in the ovaries of fetal and neonatal mice

In the present study, the expression of inhibin/activin subunits in the mouse ovary from 13 days post-coitus (dpc) to 30 days postpartum (dpp) was investigated. Circulating FSH, LH, inhibin A, and inhibin B in neonatal to 30 dpp ovaries were measured. Inhibin/activin subunits (alpha, beta(A), beta(B) ) were weakly stained in 13 dpc ovarian stromal cells and increased with age. Inhibin alpha subunit was immunolocalized in follicular granulosa cells at each developmental stage. In 30 dpp ovaries, several large antral follicles were strongly stained for inhibin alpha subunit. Inhibin beta(A) subunit was weakly immunolocalized in granulosa cells until 20 dpp. Moreover, 2 to 3 antral follicles from 20 to 30 dpp were strongly stained for inhibin beta(A) subunit. There was relatively high immunoactivity for inhibin beta(B) subunit in neonatal to 30 dpp mouse ovaries. All three inhibin subunits were stained in theca-interstitial cells from 15 dpp onward. RIA data showed that a temporal increase in circulating FSH occurred around 10 dpp, while the plasma concentrations of LH were sustained at a relatively higher level from 8 to 15 dpp. Inhibin B was detectable in circulation early at 1 dpp (day of birth), and a clear increase in inhibin B occurred around 8 dpp. Circulating inhibin B gradually increased from 20 dpp to 30 dpp, indicating a negative correlation with FSH. Inhibin A levels were only measured on 25 and 30 dpp, and the levels were low. These results suggest that inhibins play an important role in early folliculogenesis in mice. In addition, inhibin B seems to be the main functional isoform from the neonatal to prepubertal stage in the mouse ovary.     

Ontogeny of testicular inhibin and activin in ducks: An immunocytochemical analysis

The ontogeny of testicular inhibin/activin in ducks was investigated. Testicular localization of three inhibin/activin subunits (α, β_A and β_B) was determined in embryonic and newly hatched ducks from 12 days of incubation to 1 day of age, in immature ducks and in adult ducks. In the duck embryonic testis, positive α‐subunit immunostaining was first detected in the Leydig cells and Sertoli cells on day 15 of incubation, whereas β_A‐subunit and β_B‐subunit immunostaining were found in Sertoli cells and primary germ cells on day 18 of incubation. In 1 month old ducks, intense staining of α‐subunit was present in the seminiferous epithelium consistent with localization in Sertoli cells and primary germ cells, and the immunostaining of the β_A‐ and β_B‐subunit was also present in Sertoli cells and primary germ cells. Specific immunostaining with inhibin/activin α‐, β_A‐ and β_B‐subunits antisera occurred in Sertoli cells in the adult duck testes. In conclusion, it was shown that, in the duck testis, the majority of α‐, β_A‐ and β_B‐subunits are colocalized in Sertoli cells with a certain degree of staining in germ cells and the α‐subunit is present in Leydig cells of embryonic testes before day 18 of incubation. These results indicate that Sertoli cells and possibly germ cells in the embryonic testes of late stage of incubation and newly hatched ducks, immature ducks and mature ducks may produce bioactive inhibin dimers, inhibin A and inhibin B, as a possible regulator of follicle‐stimulating hormone secretion. Free inhibin/activin subunits and their dimers may also play an autocrine/paracrine role in the development of the testis and spermatogenesis. Furthermore, early onset of the α‐subunit in duck testes indicates that it may have an autocrine/paracrine effect on steroid hormones, which is important for sex differentiation.     

Glucagon‐related peptides and the regulation of food intake in chickens

The regulatory mechanisms underlying food intake in chickens have been a focus of research in recent decades to improve production efficiency when raising chickens. Lines of evidence have revealed that a number of brain‐gut peptides function as a neurotransmitter or peripheral satiety hormone in the regulation of food intake both in mammals and chickens. Glucagon, a 29 amino acid peptide hormone, has long been known to play important roles in maintaining glucose homeostasis in mammals and birds. However, the glucagon gene encodes various peptides that are produced by tissue‐specific proglucagon processing: glucagon is produced in the pancreas, whereas oxyntomodulin (OXM), glucagon‐like peptide (GLP)‐1 and GLP‐2 are produced in the intestine and brain. Better understanding of the roles of these peptides in the regulation of energy homeostasis has led to various physiological roles being proposed in mammals. For example, GLP‐1 functions as an anorexigenic neurotransmitter in the brain and as a postprandial satiety hormone in the peripheral circulation. There is evidence that OXM and GLP‐2 also induce anorexia in mammals. Therefore, it is possible that the brain‐gut peptides OXM, GLP‐1 and GLP‐2 play physiological roles in the regulation of food intake in chickens. More recently, a novel GLP and its specific receptor were identified in the chicken brain. This review summarizes current knowledge about the role of glucagon‐related peptides in the regulation of food intake in chickens.     

The regulation of food intake and correlated energy balance in mice.

In order to study the regulation of food intake and correlated body energy metabolism, the effect of restricted feeding during the light period in female IVCS mice was investigated. Access to food and water was restricted (RF group) for 3 weeks only from 10:00 hr to 17:00 hr, and that in the control group remained ad libitum. After starting food restriction (day 1), mean food intake decreased to 10% of the control value, then rose sharply, over the next 3 days, to reach 70% of the control value. Then, it decreased gradually to about 50% of the control value and remained at this low level thereafter. There was no significant difference between mean body weights for the two groups. Feed-efficiency was considered, therefore, to be higher in the RF than in the control group. RF-treatment increased plasma corticosterone levels and decreased locomotor activity. However, the diurnal patterns of plasma corticosterone levels and locomotor activity observed suggest that the circadian rhythm, synchronized with the light-dark cycle, persisted during RF-treatment. These findings suggest that restricted feeding during the naturally inactive phase (light period) induces a decrease in food intake. Animals seem to adapt to underfeeding, at least partly, by increasing feed-efficiency and plasma corticosterone levels and decreasing locomotor activity.     

Effects of food intake regulation on the energy metabolism of laying hens

1. The effects of dietary energy restriction on the energy metabolism of post‐peak‐of‐lay hens of two hybrid layer strains were studied by indirect calorimetry.

2. Starving and resting rates of heat production (SHP and RHP) were measured, over 1‐d periods, at intervals during a 25‐week period in which the experimental birds were individually restricted to 80% of their previous energy intake ad libitum.

3. In both strains mean RHP per bird was about 7% lower in the restricted birds than in controls fed ad libitum, but when RHP was expressed in terms of metabolic body size (kg^0.75) the two groups did not differ.

4. Mean SHP per bird was about 18% lower in the restricted birds of both strains than in the corresponding controls; the decrease in SHP per kg^0.75 was 12%.

5. Heat increment of feeding and calculated maintenance energy were higher, and net availability of metabolisable energy for maintenance and production was lower, in the restricted than in the control groups.

6. Gross efficiencies of egg production, in terms of both mass and energy, increased in the restricted birds.

7. Live‐weight and total carcass energy after 25 weeks of restriction were respectively about 15% and 30% lower in the restricted groups of both strains than in the groups fed ad libitum.     

Involvement of corticosterone in food intake, food passage time and in vivo uptake of nutrients in the chicken (Gallus domesticus)

To evaluate the effect of corticosterone on nutrient transport, 10-week-old male chickens were grouped in 4 categories and treated as follows: sham-operated, adrenalectomised, corticosterone (4 mg/kg injected subcutaneously for 5 d) in both sham-operated and adrenalectomised. The food intake, food passage time and uptake of calcium, phosphorus and glucose were determined by standard procedures. Corticosterone administration to both sham-operated and adrenalectomised groups stimulated significantly higher food intake, delayed food passage time and increased uptake of calcium, phosphorus and glucose, as compared to sham-operated control and adrenalectomised groups. Corticosterone administration increased absorption of these nutrients significantly more in the adrenalectomised group than in the sham-operated controls. Corticosterone also significantly elevated the plasma concentrations of these nutrients. The responses to the hormone were significantly greater in adrenalectomised birds. It is concluded that corticosterone increases food intake and retention and the absorption of calcium, phosphorus and glucose in the alimentary tract.     

Effect of water: food intake ratios in laying hens on food metabolisable energy

It has been hypothesised that a relatively high water intake results in a lower food digestibility. The influence of water:food ratios on the metabolisability of a diet was investigated. With ad libitum water and food the water:food ratios varied between 1.17 and 2.47 and showed a positive relationship with metabolisable energy. In groups of hens receiving 40 g food and water sufficient to provide water:food ratios of 1, 2, 3 and 4, the results showed a non-significant negative regression of apparent metabolisable energy with water:food ratios.     

Effect of laying on food and water intake in dwarf and normal hens

1. Irrespective of whether the hen carried the dwarfing gene, dw, food intake on days when there was ovulation and oviposition was higher than on days when there was only oviposition.

2. The “ overconsumption “ in dw hens was greater than in the Dw hens.

3. Food intake and shell thickness were correlated, the relationship being particularly close in dw hens.

4. There was a consistent and positive correlation between food intake and weight of egg laid on the same day in both Dw and dw hens.     

Immunolocalization of inhibin/activin subunits in the shiba goat fetal, neonatal, and adult testes

The objective of this study was to investigate the cellular immunolocalization of inhibin alpha and inhibin/activin (betaA and betaB) subunits in the fetal, neonatal and adult testes of Shiba goats. The testes were obtained from a fetus at 90 days, a neonate at 15 days, and two adult Shiba goats (both of 3 years old). The sections of testes were immunostained by the avidin-biotin-peroxidase complex method (ABC) using polyclonal antisera raised against porcine inhibin alpha, inhibin/activin betaA, and inhibin/activin betaB. Inhibin alpha and inhibin/activin (betaA and betaB) subunits were expressed in Leydig cells, but not in the Sertoli cells of the fetus with a weak immunostaining. An increase in the number of positive cells and a more intense immunohistochemical signal for inhibin alpha and inhibin/activin (betaA and betaB) subunits were observed in the Leydig cells of neonatal testes. Moreover, inhibin alpha, betaA, and betaB subunits were expressed in the Sertoli cells and Leydig cells of adult testes, respectively. These results suggest that Shiba goats testes have the ability to synthesize inhibins in the fetus, neonate, and adult, and the cellular localization of inhibin/activin subunits showed age-related changes in fetal, neonatal, and adult testes of Shiba goats.     

黑皮质素受体4对采食和能量代谢调控机制的研究进展

黑皮质素受体(MCRs)有5种亚型(MC1R~MC5R),在机体各组织中分布,具有不同的生理功能。其中主要参与采食和能量代谢调节的受体是黑皮质素受体4(MC4R),它能够通过多条信号通路调节采食和能量代谢,并且在由MC4R突变体介导的2条信号传导通路中观察到由同一配体引起的偏置信号传导。本文综述了MC4R对动物采食和能量代谢的调控作用及机制,并阐述了MC4R突变对其功能的影响。     

The relationship of food intake during growth and food intake at maturity with lactation food intake in a mouse model

Selection for increased leanness and improved food efficiency in pigs has resulted in a decreased voluntary food intake. It has been argued that voluntary food intake during lactation should be considered in sow breeding programmes. The aim of the present study was to investigate the phenotypic correlation of food intake during growth and food intake at maturity with maximum lactation food intake in a mouse model. A total of 179 records were available on female mice selected for litter size at birth (S-line) and non-selected control females (C-line) from 3 weeks of age to 21 days in lactation. Half of the litters were standardized to eight pups per litter (s) and half were not standardized (ns). Growth intake was measured as the average intake between 21 and 42 days of age, mature intake was measured from a linear regression of food intake against age between 42 and 69 days of age, and lactation intake was measured as a linear regression of food intake against days in lactation between 5 and 14 days in lactation. In both lines, females with a higher growth intake also had a higher mature intake (r = 0.63 to 0.75, P < 0.0001). Lactation intake was related with growth intake and mature intake in Sns females (r = 0.50 and 0.46, P < 0.01) and with growth intake in Ss females (r = 0.32, P < 0.05). In both lines, lactation intake was highly correlated with litter weight (r = 0.48 to 0.94, P < 0.001). Sns and Ss females with higher growth intake supported larger litter weights during lactation (r = 0.32 and 0.30, respectively, P < 0.05) and Sns females with higher mature intakes tended to support larger litter weights (r = 0.28, P = 0.060). It is suggested that lactating C-line females eat to support a given litter size, while S-line females support the maximum litter weight that is allowed for by their intake capacity, and still produce at high levels when litters are standardized. Since lactating sows mobilise body reserves, the relationship of food intake during growth with that during lactation may be reflected in the relationship between growth intake and body condition.     

Involvement of thalamic paraventricular nucleus in the anticipatory reaction under food restriction in the rat

To investigate which brain regions are involved in the anticipatory activity in rats restricted feeding for 2 hr, we examined c-Fos expression before and after feeding. Only the thalamic paraventricular nucleus (tPVN) showed c-Fos expression before feeding than after feeding. After the anticipatory locomotor activity rhythm was established, lesioning the tPVN attenuated this rhythm, but not the light-dark entrained rhythm. The anticipatory increase of blood corticosterone levels was not established in long-term tPVN-lesioned rats. These results suggest that the tPVN is involved in the expression of anticipatory reactions under a food-restricted regimen.     

The relationship between food and water intake and the effects of water restriction on laying brown leghorn hens

1. In 10 laying Brown Leghorn hens, hourly patterns of food and water intake followed each other closely, both throughout the day and in relation to oviposition time.

2. Only half the birds showed significant (P < 0.05) positive correlations between food and water intake on a daily basis, but all of them showed highly significant correlations on an hourly basis. However, on average, about 20% of both the daily and the hourly variation in water intake could be accounted for by variation in food intake, and vice versa.

3. Restricting the daily water supply of each bird to 90% of its ad libitum intake, for a period of 6 weeks, caused a predicted reduction in daily food intake with only 3 out of 10 birds, but a very precise reduction to the level predicted with the overall mean food intake of all the birds. This suggests that water restriction may be a good way of controlling the food consumption of groups of birds but not of individuals.

4. Although egg production did not differ significantly between the ad libitum and water restriction periods, it did decline in the second half of the restriction period, at a time when the birds were gaining weight. This appears to confirm the widely‐held view that water restriction cannot be used to control the body weight of laying birds without it first affecting egg production. It is concluded that water restriction has little or no practical application for layers, but may be of value for reducing the growth rate of young birds in order to delay sexual maturity.