Induction of ventrolateral hypothalamic fatty acid oxidation in diabetic rats

Diabetic rats were used to test a previous hypothesis that alterations in ventrolateral hypothalamic (VLH) fatty acid oxidation observed in over- and underfed rats were a function of the animals' peripheral energy balance and not merely a function of their energy intake. Standard adaptations to the diabetic condition were exhibited in streptozotocin diabetic rats such as depressed body weights, hyperphagia and hyperglycemia, elevated serum free fatty acids, depressed insulin concentrations, depressed hepatic glucose oxidation and elevated hepatic fatty acid oxidation. Rates of VLH fatty acid oxidation to CO2 and to an acid, water-soluble fraction in diabetic rats were elevated relative to non-diabetic rats. The alterations in VLH fatty acid oxidation in diabetic rats were similar to changes previously observed in animals exhibiting a negative energy balance. The results were discussed with respect to the concept that VLH fatty acid oxidation was a component in the recognition of peripheral energy balance and, in part, served to alter the regulators of energy balance and food intake.     

Effect of fasting on the metabolism in rat aorta

The oxidation of 14C-labelled glucose, beta-hydroxybutyrate and palmitate to CO2 and the incorporation of 14C-labelled amino acid into alkali-soluble protein were studied in aorta from fed and fasted male Sprague-Dawley rats, weighting about 200 g. Substrate oxidation and amino acid incorporation were measured during incubation of rat aorta in vitro for 2-3 h. After fasting for 6 h there was a slight but significant increase in the plasma concentration of beta-hydroxybutyrate. Blood glucose was lowered after 12 h while an increase in the plasma concentration of free fatty acids was found after 24 h. A decrease in the oxidation of glucose in rat aorta was found after fasting for 12 h and with prolonged fasting a further decrease in the aortic glucose oxidation was found. After fasting for 4 days the oxidation of beta-hydroxybutyrate and the incorporation of 14C-leucine and 14C-phenylalanine into protein were reduced in rat aorta while the oxidation of palmitate was not altered. The effects of fasting on substrate oxidation and amino acid incorporation in rat aorta, found in this study are similar to the known effects of diabetes on vascular metabolism.     

Regulation of hepatic free fatty acid metabolism by glucagon and insulin.

The roles of glucagon and insulin in the direct short-term regulation of hepatic free fatty acid (FFA) metabolism were studied in hepatocytes isolated from fed, fasted, and streptozotocin-induced diabetic rats. In fed animals, the principal metabolic product of palmitate metabolism was triglyceride, whereas ketones were the major product in fasted and diabetic animals. Glucagon at physiological concentrations increased ketogenesis and decreased triglyceride synthesis from palmitate in hepatocytes from fed rats at FFA concentrations 1.0 mM or less. Insulin had no effect on FFA metabolism when present as the sole hormone, but could antagonize the actions of submaximal concentrations of glucagon. The metabolism of palmitate in fasted or diabetic hepatocytes was unaffected by either hormone. Ketogenesis from octanoate was also unaffected by hormone addition in all cell types. These data are consistent with a locus of hormonal regulation at a step prior to beta-oxidation of fatty acid. Glucagon and insulin may modulate FFA metabolism by both intrahepatic and extrahepatic mechanisms.     

Effects of oleic acid on distinct populations of neurons in the hypothalamic arcuate nucleus are dependent on extracellular glucose levels

Pharmacological manipulation of fatty acid metabolism in the hypothalamic arcuate nucleus (ARC) alters energy balance and glucose homeostasis. Thus, we tested the hypotheses that distinctive populations of ARC neurons are oleic acid (OA) sensors that exhibit a glucose dependency, independent of whether some of these OA sensors are also glucose-sensing neurons. We used patch-clamp recordings to investigate the effects of OA on ARC neurons in brain slices from 14- to 21-day-old Sprague-Dawley (SD) rats. Additionally, we recorded spontaneous discharge rate in ARC neurons in 8-wk-old fed and fasted SD rats in vivo. Patch-clamp studies showed that in 2.5 mM glucose 12 of 94 (13%) ARC neurons were excited by 2 microM OA (OA-excited or OAE neurons), whereas six of 94 (6%) were inhibited (OA-inhibited2.5 or OAI2.5 neurons). In contrast, in 0.1 mM glucose, OA inhibited six of 20 (30%) ARC neurons (OAI0.1 neurons); none was excited. None of the OAI0.1 neurons responded to OA in 2.5 mM glucose. Thus OAI2.5 and OAI0.1 neurons are distinct. Similarly, in seven of 20 fed rats (35%) the overall response was OAE-like, whereas in three of 20 (15%) it was OAI-like. In contrast, in fasted rats only OAI-like response were observed (three of 15; 20%). There was minimal overlap between OA-sensing neurons and glucose-sensing neurons. In conclusion, OA regulated three distinct subpopulations of ARC neurons in a glucose-dependent fashion. These data suggest that an interaction between glucose and fatty acids regulates OA sensing in ARC neurons.     

Cholecystokinin concentration in specific brain areas of rats fed during the light or dark phase of the circadian cycle

Measurement of peptide concentration in specific areas can be used as an initial investigative method for identifying brain sites in which the peptides may be acting. In this study cholecystokinin (CCK) concentration in specific hypothalamic and hindbrain areas of male Sprague-Dawley rats was measured in order to determine whether changes occurred as a result of feeding activity during different portions of the circadian cycle. Three groups of 40 rats each were studied: Group 1 were fasted 16 hr during the dark phase then sacrificed immediately or after a 20 min light phase meal. Group 2 were fasted 16 hr during the light phase then sacrificed immediately after lights out or after a 20 min dark-onset meal. Group 3 were fed ad lib and sacrificed immediately after light out or after a 20 min dark-onset meal. CCK was extracted from dissected areas and concentration was measured by RIA. There was no difference in CCK concentration of any of the 9 brain areas in rats fasted during the dark phase and fed during the light phase. In rats fasted during the light phase CCK concentration of the paraventricular nucleus (PVN) was greater in those that subsequently ate a meal at dark-onset than in those that did not eat (p less than 0.05). In ad lib fed rats CCK concentration was less in the anterior hypothalamus (AH) and greater in the supraoptic nucleus (SON) in rats that ate a dark-onset meal than in rats that did not (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

D-galactosamine hepatotoxocity. V. Role of free fatty acids in the pathogenesis of fatty liver

The role of free fatty acids (FFA) in the pathogenesis of fatty liver was investigated in female rats who received a single ip injection of d-galactosamine-HCl, (GalN), 750 mg/kg body weight. Groups of rats were either fasted for 14 hr prior to GalN injection and then fasted for the duration of the experiment or were fed ad libitum prior to and after GalN administration. Plasma FFA were determined in groups of fasting or fed rats sacrificed at intervals between 0 and 24 hr after GalN administration. The results revealed a progressive increase in plasma FFA in GalN-injected fasted rats (0 hr, 0.40 μmol/ml; 24 hr, 1.09 μmol/ml) whereas in fed animals only a modest increase in plasma FFA concentrations occurred. Hepatic triglyceride content was determined in groups of fasted and fed rats at 6 and 24 hr after GalN administration. Hepatic triglycerides, in fasted rats, were increased 7-fold at 6 hr (22.4 ± 8.5 mg/g) and were markedly increased at 24 hr (114.8 ± 18.4 mg/g). In contrast, feeding protected the rats from the development of fatty liver since hepatic triglycerides were only twice controls at 6 hr and 4-fold increased 24 hr after GalN. Ultrastructural studies were performed at 15, 24, and 48 hr after GalN in fed and fasted rats. Electron microscopy disclosed hepatocellular necrosis and profound fat accumulation in the fasted animals; however, feeding afforded marked protection against the development of fatty liver and hepatic injury. The results of these studies indicate that the GalN-induced fatty liver is associated with a sustained elevation of plasma FFA. The increase in plasma FFA can be prevented by feeding the animals prior to and after GalN administration suggesting that a stimulus for FFA elevation may be the alterations in carbohydrate metabolism known to be induced by GalN in rat liver.     

Meal-stimulated increased concentrations of CCK in the hypothalamus of Zucker obese and lean rats

CCK is a putative satiety peptide found to be active when administered peripherally and centrally. Concentrations of CCK have been measured in the brains of fed and fasted animals, but as yet no clear correlation with feeding has been found. In the present experiment rats were sacrificed after a 6-hr fast or 5 min after a meal. Areas of the hypothalamus were removed from these rats and assayed for CCK content. The relationship between obesity and CCK content in specific areas of the brain was also investigated by using Zucker obese and lean rats. In fed rats the CCK concentrations were higher than in fasted rats in the ventromedial hypothalamus (VMH) (56 vs. 42 pg/mg tissue, p less than 0.005), lateral hypothalamus (38 vs. 27 pg/mg, p less than 0.01) and supraoptic nucleus (48 vs. 39 pg/mg, p less than 0.01). In obese rats the concentrations were higher than in lean rats in the VMH (56 vs. 41 pg/mg, p less than 0.003), dorsal medial hypothalamus (37 vs. 30 pg/mg, p less than 0.04) and anterior hypothalamus (61 vs. 37 pg/mg, p less than 0.001). Average concentrations of CCK in all hypothalamic areas were higher in females than males (50 vs. 40 pg/mg, p less than 0.001). Thus, CCK concentrations in specific areas of the hypothalamus increased with feeding, supporting the potential role of CCK in the central nervous system as a satiety peptide. Further, although the concentrations of CCK in obese rats were higher than those in lean rats, the changes in CCK concentration with feeding were the same, showing that obesity is not a consequence of decreased concentrations or concentration changes of CCK in brain.     

Modulation by corticotropin-releasing factor of monoamine metabolism in the lateral hypothalamus

Corticotropin-releasing factor (CRF) was injected into the lateral hypothalamus of conscious unrestrained rats and the local concentration of monoamines in the vicinity of the microinjection monitored by microdialysis. The concentration of norepinephrine and MHPG in the dialysis fluid from the lateral hypothalamic areas of rats fasted for 24 h was nearly 4 times higher than in fed rats. Following the injection of 2 micrograms of CRF into the lateral hypothalamus of fasted rats there was a rapid decline in levels of both norepinephrine and 3-methoxy-4-hydroxyphenylglycol (MHPG) to the level in fed rats after 60-90 min. The changes in MHPG and norepinephrine in the fed rats were not significant There was no difference in serotonin concentration between fasted and fed animals, although the mean value for 5-hydroxyindoleacetic acid (5-HIAA) was slightly increased. Following the injection of CRF, there was a fall in serotonin in the fed rats but not in the fasted animals. There was a fall in the concentration of 5-HIAA in both the fasted and fed rats so that at 30, 60 and 90 min their concentrations were not significantly different. The concentration of DOPAC in the lateral hypothalamus was twice as high in the fasted as in the fed rats. Following injection of CRF there was a rapid decline in DOPAC concentrations in the fasted rats and a small decline in the fed rats. By the end of 30 min after the injection of CRF, concentrations of DOPAC were similar in fed and fasted rats.(ABSTRACT TRUNCATED AT 250 WORDS)     

RNA content of neurons in the ventromedial nuclei and lateral hypothalamic area relative to feeding status

The total RNA content of hypothalamic and cortex neurons in relation to the feeding status of adult male Wistar rats was studied. Experimental conditions including food deprivation (12 and 24 hours) and relative satiation (short-term refeeding, glucose or glycerol administration) changed in different ways the total RNA content of the neurons in the ventromedial hypothalamic nuclei (VMH) and in the lateral hypothalamic area (LHA) with respect to fasting or satiety. Only the long-term absence of food (24 hours) significantly increased the total RNA content of the VMH cells, while the RNA content of the LHA neurons significantly decreased in both the 12 and 24 hr fasted rats compared with those fed ad lib. The sixty minute free access to food after 12 or 24 hours of fasting fully reversed these changes. The short-term food intake significantly increased the RNA content of the LHA cells of the 12 and 24 hr fasted animals while the total RNA content of the VMH neurons significantly decreased only in the 24 hr fasted rats. The effect of glucose and glycerol administration on the RNA content of the LHA neurons (in 12 hr fasted rats) was similar to the effect of refeeding. One hour after giving glucose (1 g/kg b.wt.) or glycerol (300 mg/kg b.wt.) the total RNA content in the LHA neurons significantly increased. No changes in RNA content were observed in the neurons of the cortex when comparing the experimental and control rats. The results demonstrated the close relationship between the RNA content of the hypothalamic neurons and the feeding status.(ABSTRACT TRUNCATED AT 250 WORDS)     

罗格列酮对2型糖尿病心肌能量底物代谢的影响

目的：探讨在2型糖尿病中胰岛素抵抗(IR)对心肌能量底物代谢以及心功能的影响。 方法： 采用高脂喂养(40％脂肪、42％碳水化合物和18％蛋白)4周及链脲佐菌素(STZ，35 mg/kg)1次性腹腔注射建立2型糖尿病大鼠模型，成模后随机分为2组：实验对照组(fat-fed/STZ)继续高脂喂养，实验治疗组(fat-fed/STZ/RSG)给予罗格列酮(RSG) 3 mg·kg-1·d-1治疗2周；正常对照组(chow-fed)为普通饮食喂养(12％脂肪、60％碳水化合物和28％蛋白)。左室插管检测心功能后进行30 min等容离体心脏灌注，灌注液含100 μU胰岛素、3％BSA、5 mmol/L葡萄糖、0.4 mmol/L［3H］软脂酸，测定样品葡萄糖摄取量及［3H2O］计数，评估葡萄糖和脂肪酸氧化率。 结果： 高脂喂养加小剂量STZ所制备模型鼠的血糖、血浆胰岛素及FFA水平均高于正常鼠,与临床2型糖尿病的代谢特征相似。成模2周后，fat-fed/STZ组大鼠与chow-fed组比较，30 min心肌葡萄糖总氧化量明显减少［(54.7±6.2 vs 69.0±5.7)μmol/g干重，P<0.01］。葡萄糖氧化率由25％降至18％，脂肪酸氧化率由75％增加到82％；同时，心功能检查显示左室EDP明显增加［(14.3±1.8 vs 10.5±1.1) mmHg，P<0.05］，-dp/dtmax降低［(550±57 vs 650±42) mmHg/s，P<0.01］，而+dp/dtmax无明显改变。与fat-fed/STZ组比较，fat-fed/STZ/RSG组大鼠的血糖明显改善［(9.0±4.6 vs 15.1±3.3) mmol/L，P<0.01］，血浆胰岛素减少(P<0.05)，FFA降低［(2.2±0.8 vs 3.3±0.8) mmol/L, P<0.05］；心肌葡萄糖的总氧化量升高到(63.5±6.4)μmol/g。干重，葡萄糖和脂肪酸的氧化率分别为24％和76％，基本达到chow-fed组水平(P>0.05)；EDP和-dp/dtmax均得到明显的改善(P<0.05)。 结论： IR导致2型糖尿病心肌能量底物代谢的异常和左室舒张功能的降低，早期使用RSG改善IR，不仅能提高心肌对葡萄糖的利用、降低脂肪酸氧化，也有助于改善心功能。     

控制血糖促进糖尿病大鼠心肌葡萄糖代谢

目的 观察控制血糖对2型糖尿病大鼠心肌能量代谢的影响.方法 18只SD雄性大鼠随机分为对照组(6只)、糖尿病组(6只)和治疗组(6只).采用高脂喂养及腹腔注射链脲佐菌素建立2型糖尿病大鼠模型,应用离体心脏Langendorf灌注,测定心肌葡萄糖氧化率;采用Western blot法检测心肌细胞GLUT4的表达.结果 糖尿病组大鼠心肌葡萄糖总氧化量较对照组减少(P相似文献   

Amino acid degradation and effect of leucine on pyruvate oxidation in rat atrial muscle

Both left and right atria from fasted rats produced significant amounts of 14CO2 during incubation with U-14C-labeled leucine, isoleucine, valine, alanine, glutamate, glutamine, aspartate, asparagine, proline, threonine, or lysine. This pattern of amino acid metabolism resembles that of skeletal muscle. Production of 14CO2 from [1-14C]leucine was 2.5-fold greater in atria from fasted than from fed rats and was due to greater alpha-ketoisocaproic dehydrogenase activity in the tissue from fasted animals. At normal plasma concentrations, leucine reduced the oxidation of glucose and lactate in atria from fasted but not from fed rats by inhibiting pyruvate oxidation and without altering the rate of glycolysis. Leucine also reduced glucose oxidation when added in the presence of ketone bodies or other amino acids and stimulated the release of lactate into the medium. Although the leucine skeleton can be completely oxidized to CO2 and thus can serve as an alternative fuel in fasting in place of glucose, oxidation of leucine (like glucose or lactate oxidation) accounts only for a very small fraction of the total oxygen consumption of the resting atria.     

Metabolic characteristics of skeletal muscle from lean and obese Zucker rats

The purpose of this study was to determine if the metabolic response to obesity and to pair feeding of obese Zucker rats to lean Zucker rats was similar across skeletal muscles. Oxidation of glucose, palmitate and isoleucine was studied in muscle strips in vitro using appropriate 14- carbon substrates as tracers. The plantaris muscle was subjected to histochemical analyses using an alkaline actomyosin ATPase, NADH-tetrazolium reductase and an oil red 0 stain. Soleus muscles from both ad libitum and pair fed obese rats oxidized less glucose to CO2, but released similar amounts of lactate when compared to the soleus muscles of lean rats. Oxidation of glucose was similar in the extensor digitorum longus (EDL) muscle of ad libitum fed obese rats, but lower when pair fed to the intake of lean rats. No differences were apparent in palmitate oxidation to CO2 or in incorporation into lipid (both soleus and EDL muscles), except in the EDL muscle of pair-fed obese rats which exhibited a higher rate for palmitate metabolism when compared with lean rats. Isoleucine oxidation to CO2 was higher in the EDL and plantaris muscles, but similar in the soleus muscle of ad libitum-fed obese rats when compared with lean rats. The magnitude of the difference in isoleucine oxidation was similar when the obese rats were pair fed. No differences in the percentage of plantaris muscle fibers sensitive to alkaline ATPase staining were observed. The plantaris muscle of obese rats, contained a higher proportion of oxidative fibers. These results indicate the great risk in generalizing about metabolic activity of the whole skeletal muscle mass based on observations made on one, or even two, distinct muscles in this animal model. Also, pair feeding of obese to lean Zucker rats did not result in uniform changes in metabolism between muscles of the obese rats.     

Changes in brain CCK concentrations with peripheral CCK injections in Zucker rats

Evidence suggests that the satiety responses to peripherally administered CCK are mediated by a CNS component(s). Since CCK concentrations in the hypothalamus can change with degree of hunger, they may also be involved in the feeding response to peripherally administered CCK. Six-hr fasted rats were administered saline or 2 micrograms/kg CCK-8 and half were allowed to eat a meal. They were sacrificed after a meal or after the fast and hypothalamic content of CCK was measured by RIA. In rats injected with CCK, compared with those injected with saline, CCK concentrations were decreased in the ventromedial hypothalamus (VMH, 39 vs. 47 pg/mg tissue, p less than 0.004) and dorsomedial hypothalamus (17 vs. 21 pg/mg, p less than 0.009) and increased in the lateral hypothalamus (28 vs. 19 pg/mg, p less than 0.01). CCK concentrations in fed compared with fasted rats were higher in the VMH (47 vs. 39 pg/mg, p less than 0.002) and in obese compared with lean rats CCK concentrations were higher in the paraventricular nucleus (48 vs. 38 pg/mg, p less than 0.05), suprachiasmatic nucleus (46 vs. 34 pg/mg, p less than 0.008) and VMH (52 vs. 34 pg/mg, p less than 0.001). Since peripheral injections of CCK influenced concentrations of CCK in hypothalamic areas associated with feeding, these results provide evidence that the feeding response to peripherally injected CCK may be mediated by changes in CCK content of specific brain areas.     

Rapid changes in the sensitivity of arcuate nucleus neurons to central ghrelin in relation to feeding status

Ghrelin, the endogenous ligand for the growth hormone secretagogue (GHS) receptor, stimulates feeding and increases body weight. Systemic ghrelin administration induces the immediate-early gene protein product, c-Fos, in the arcuate nucleus of the hypothalamus (ARC) of satiated rats and this increase is potentiated in fasted rats. The aim of this study was to determine whether potentiation was seen in fasted animals after intracerebroventricular (i.c.v) administration of ghrelin and to identify the hypothalamic nuclei activated by this peptide. In addition we investigated if allowing fasted animals to re-feed for 1 h prior to i.c.v. ghrelin injection affected the c-Fos response. Using c-Fos immunocytochemistry, we demonstrated that i.c.v. ghrelin activated several hypothalamic nuclei, including the ARC, paraventricular nucleus (PVH) and the lateral hypothalamus (LH). The c-Fos response was greater in fasted animals compared with satiated animals. Fasted rats allowed access to food for 1 h prior to central ghrelin administration showed an attenuated response in the ARC, similar to the response seen in fed animals. However, the response in the LH (including in the orexin neurons) was further potentiated. The latter may reflect a connection between the hypothalamus and regions of the brain responding to the reward value of the meal.     

Lipid metabolism in human skeletal muscle cells: effects of palmitate and chronic hyperglycaemia

This review focuses on the effect of exogenous factors known to be of importance for the development of insulin resistance in differentiated human myotubes. Recent data from our laboratory on the effects of fatty acid pre-treatment and chronic glucose oversupply on fatty acid and glucose metabolism, without and with acute insulin are presented, and discussed in the context of other recent publications in the field. Pre-treatment of myotubes with palmitate, chronic hyperglycaemia, and acute high concentrations of insulin changed fatty acid metabolism in favour of accumulation of intracellular lipids. Acute insulin exposure increased (14)C-oleate uptake and levels of free fatty acids (FFA) and triacylglycerol (TAG). Palmitate pre-treatment further increased oleate uptake, both under basal conditions and in the presence of insulin, with a marked increase in the phospholipid (PL) fraction, with a concomitant reduction in oleate oxidation. Chronic hyperglycaemia also promoted increased lipogenesis and elevated levels of cellular lipids. Changes in fatty acid metabolism in human muscle, in particular fatty acid oxidation, are probably crucial for the molecular mechanism behind skeletal muscle insulin resistance and impaired glucose metabolism. Differentiated human skeletal muscle cells may be an ideal system to further explore the mechanisms regulating lipid metabolism.     

Role of hypothalamic 5′-AMP-activated protein kinase in the regulation of food intake and energy homeostasis

Although obesity is an epidemic threat to general health worldwide, an effective treatment has yet to be found. Insights into weight-regulatory pathways will accelerate the identification of new molecular targets for anti-obesity agents. 5-AMP-activated protein kinase (AMPK) is an enzyme activated during low cellular energy charge. In peripheral tissues, the activation of AMPK influences various metabolic pathways, including glucose uptake, glycolysis, and fatty acid oxidation, all of which help to re-establish a normal cellular energy balance. AMPK is also present in the neurons of the hypothalamus, a critical center in the regulation of energy homeostasis. Recent studies from our group and others have shown that many factors (-lipoic acid, leptin, insulin, ghrelin, glucose, 2-deoxyglucose, etc.) cause an alteration in hypothalamic AMPK activity that mediates effects on feeding behavior. Hypothalamic AMPK also appears to play a role in the central regulation of energy expenditure and peripheral glucose metabolism. These data indicate that hypothalamic AMPK is an important signaling molecule that integrates nutritional and hormonal signals and modulates feeding behavior and energy metabolism.     

The effect of controlled feeding conditions on the metabolic characteristics of rats

To evaluate the effect of feeding conditions on blood glucose, insulin and free fatty acid concentrations, rats were maintained on a 2-hr feeding/22-hr fasting (regular-fasted) schedule for 4 weeks. The animals were then subjected to glucose or insulin loads immediately prior to the usual meal time. Animals fasted for only 22 hr (single-fasted) just before the experiments, and rats having access to food ad lib were similarly loaded and tested. The results demonstrate that the regular fasting regime induces certain metabolic alterations well described in the literature for the single-fasted-period to become more pronounced, specifically, a reduction in insulin secretion and a probably increase in peripheral responsiveness to this hormone. In addition, glucose loading was more effective in lowering plasma free fatty acid concentration in rats restricted to a regular fasting scheme.     

Sweet taste receptor in the hypothalamus: a potential new player in glucose sensing in the hypothalamus

The hypothalamic feeding center plays an important role in energy homeostasis. The feeding center senses the systemic energy status by detecting hormone and nutrient levels for homeostatic regulation, resulting in the control of food intake, heat production, and glucose production and uptake. The concentration of glucose is sensed by two types of glucose-sensing neurons in the feeding center: glucose-excited neurons and glucose-inhibited neurons. Previous studies have mainly focused on glucose metabolism as the mechanism underlying glucose sensing. Recent studies have indicated that receptor-mediated pathways also play a role in glucose sensing. This review describes sweet taste receptors in the hypothalamus and explores the role of sweet taste receptors in energy homeostasis.     

Inhibition of glucose oxidation by alpha-cyano-4-hydroxycinnamic acid stimulates feeding in rats

Alpha-cyano-4-hydroxycinnamic acid (4-CIN, 100-200 mg/kg b.wt.), which impairs glucose oxidation by inhibiting pyruvate transport across the mitochondrial membrane, stimulated feeding in rats following intraperitoneal injection without affecting blood glucose level. Like 2-deoxy-D-glucose (2-DG), an inhibitor of glycolysis, 4-CIN probably acts mainly on the CNS through activation of alpha(2)-adrenergic receptors, because the feeding response to 4-CIN was eliminated by phentolamine or yohimbine. Unlike feeding elicited by 2-DG, 4-CIN-induced feeding was eliminated by total abdominal (but not hepatic branch) vagotomy. Since peripheral atropinization also blocked 4-CIN-induced feeding, activation of central parasympathetic neurons seems to be involved in 4-CIN-induced feeding. The feeding response to 4-CIN was diminished in rats fed a high-fat diet, probably because metabolic sensors sensing fatty acid oxidation counteract the feeding response to 4-CIN. The results suggest that inhibition of glucose oxidation by blocking pyruvate entry into mitochondria stimulates feeding in rats in particular when fed a high-carbohydrate diet.