Sympathetic Activity, Age, Sucrose Preference, and Diet‐Induced Obesity

Levin, Barry E.

doi:10.1002/j.1550-8528.1993.tb00622.x

Cited by 38 publications

(42 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In agreement, preliminary data from our group show that central TLQP-21 may limit immobilization-induced NE release while increasing late E release (Bartolomucci et al, unpublished observations). Alternative explanations would be that: (1) TLQP-21 may normalize the higher basal sympathetic activity described in DIO-prone rats [44,45]; (2) chronic TLQP-21 infusion may modulate pre-existing differences in adipose tissue gene expression which can predispose mouse to be probe to obesity [39].…”

Section: Discussionmentioning

confidence: 99%

Chronic intracerebroventricular injection of TLQP-21 prevents high fat diet induced weight gain in fast weight-gaining mice

et al. 2009

View full text Add to dashboard Cite

The vgf gene regulates energy homeostasis and the VGF-derived peptide TLQP-21 centrally exerts catabolic effects in mice and hamsters. Here, we investigate the effect of chronic intracerebroventricular (icv) injection of TLQP-21 in mice fed high fat diet (HFD). Fast weightgaining mice injected with the peptide or cerebrospinal fluid were selected for physiological, endocrine, and molecular analysis. TLQP-21 selectively inhibited the increase in body weight and epididymal white adipose tissue (eWAT) weight induced by HFD in control animals despite both groups having a similar degree of hyperphagia. TLQP-21 normalized the increase in leptin and decrease in ghrelin while increasing epinephrine and epinephrine/norepinephrine ratio when compared to values in controls. Finally, HFD-TLQP-21 mice showed a selective increase of eWAT b3-adrenergic receptor mRNA. Peroxisome-proliferatoractivated-receptor-d and hormone-sensing-lipase mRNA were also upregulated. In conclusion, chronic icv infusion of TLQP-21 prevented the early phase of diet-induced obesity despite overfeeding. These effects were paralleled by activation of catabolic pathways within the eWAT. Our results further support a role for TLQP-21 as a catabolic neuropeptide.

show abstract

Section: Discussionmentioning

confidence: 99%

Chronic intracerebroventricular injection of TLQP-21 prevents high fat diet induced weight gain in fast weight-gaining mice

et al. 2009

View full text Add to dashboard Cite

show abstract

“…• The outbred population of Sprague-Dawley rats contains obesity-prone (DIO-prone) and obesity-resistant (DR-prone) rats that differ in intake, body weight, and fat only when fed a diet of moderate fat and caloric density (17). DIO-prone rats have defective glucosensing (18 -20) and can be identified prospectively by their high 24-h urinary norepinephrine excretion, as compared with DR-prone rats (17).…”

mentioning

confidence: 99%

“…DIO-prone rats have defective glucosensing (18 -20) and can be identified prospectively by their high 24-h urinary norepinephrine excretion, as compared with DR-prone rats (17). Of 38 chow-fed, 3-month-old male rats, the 14 with the highest norepinephrine levels, as assessed by highperformance liquid chromatography (17), were designated as DIO-prone, and the 14 with the lowest levels were designated as DR-prone. Half of each of these groups were maintained on ad libitum chow and half were fasted for 48 h. Animals were decapitated between 0800 and 1000 h.…”

mentioning

confidence: 99%

Glucokinase Is the Likely Mediator of Glucosensing in Both Glucose-Excited and Glucose-Inhibited Central Neurons

et al. 2002

Self Cite

View full text Add to dashboard Cite

Specialized neurons utilize glucose as a signaling molecule to alter their firing rate. Glucose-excited (GE) neurons increase and glucose-inhibited (GI) neurons reduce activity as ambient glucose levels rise. Glucoseinduced changes in the ATP-to-ADP ratio in GE neurons modulate the activity of the ATP-sensitive K ؉ channel, which determines the rate of cell firing. The GI glucosensing mechanism is unknown. We postulated that glucokinase (GK), a high-Michaelis constant (K m ) hexokinase expressed in brain areas containing populations of GE and GI neurons, is the controlling step in glucosensing. Double-label in situ hybridization demonstrated neuron-specific GK mRNA expression in locus ceruleus norepinephrine and in hypothalamic neuropeptide Y, pro-opiomelanocortin, and ␥-aminobutyric acid neurons, but it did not demonstrate this expression in orexin neurons. GK mRNA was also found in the area postrema/nucleus tractus solitarius region by RT-PCR. Intracarotid glucose infusions stimulated c-fos expression in the same areas that expressed GK. At 2.5 mmol/l glucose, fura-2 Ca 2؉ imaging of dissociated ventromedial hypothalamic nucleus neurons demonstrated GE neurons whose intracellular Ca 2؉ oscillations were inhibited and GI neurons whose Ca 2؉ oscillations were stimulated by four selective GK inhibitors. Finally, GK expression was increased in rats with impaired central glucosensing (posthypoglycemia and diet-induced obesity) but was unaffected by a 48-h fast. These data suggest a critical role for GK as a regulator of glucosensing in both GE and GI neurons in the brain. S pecialized neurons utilize glucose as a signaling molecule rather than as an energy substrate. Glucose-excited (GE) neurons increase, whereas glucose-inhibited (GI) neurons decrease, their firing rate as ambient glucose levels rise (1-3). It is unclear how GI neurons sense glucose, but GE neurons function much like the pancreatic ␤-cell, which utilizes the ATPsensitive K ϩ (K ATP ) channel to sense glucose and regulate insulin secretion (2-7). Although many neurons contain K ATP channels, few exhibit glucosensing properties (8,9). This makes control of glycolysis a major candidate as a regulator of ATP production and K ATP channel activity (6). The pancreatic form of glucokinase (GK; hexokinase IV, ATP:D-glucose 6-phosphotransferase) is selectively expressed in brain areas where glucosensing neurons reside (5,10 -12). GK has the physiological properties that would make it an ideal regulator of glucosensing in neurons (6,13). Previous studies examined a role for GK in hypothalamic glucosensing neurons in brain slice preparations, where presynaptic inputs could not be excluded, and under conditions outside the physiological range of brain glucose (4,5). The current studies provide new data on the neurotransmitter and peptide phenotype of neurons expressing GK, the regulatory role of GK in isolated hypothalamic GE and GI neuron activity, and the in vivo conditions associated with altered brain GK expression. RESEARCH DESIGN AND METHODSAnimals. All ...

show abstract

“…5,6 We used outbred Sprague-Dawley rats to more closely model human populations, but, because rats do not survive hepatocyte collection, it was necessary to identify and preselect OP and OR rats before feeding a high-fat diet. Rats eating a low-fat diet can be screened for susceptibility to diet-induced obesity on the basis of urinary catecholamine excretion 8 or whole body oxidation of radiolabeled fatty acid; 5 however, the procedures and equipment involved are complicated, inconvenient and not commonly available. Instead, we used a relatively simple procedure based on previous observations that under certain circumstances fasting plasma triglyceride levels in low-fat-fed rats are predictive of subsequent weight gain after animals are switched to a high-fat food.…”

mentioning

confidence: 99%

Reduced hepatocyte fatty acid oxidation in outbred rats prescreened for susceptibility to diet-induced obesity

Hong

Friedman

2008

Int J Obes

View full text Add to dashboard Cite

Rats vary in their propensity to become obese when eating a high-fat diet, but the factors that make some rats susceptible and others resistant to diet-induced obesity are unclear. Recent studies show that rats predisposed to diet-induced obesity have a preexisting deficit in fat oxidation and suggest that this impairment is due in part to reduced fatty acid oxidation in liver. To determine directly whether rats susceptible to diet-induced obesity are less able to oxidize fatty acids in liver, we measured palmitate oxidation in hepatocytes isolated from outbred Sprague-Dawley rats that were identified while still eating a low-fat diet as obesity-prone or obesity-resistant by using a new screening procedure based on the change in plasma triglyceride concentration produced by an intragastric load of a fat and carbohydrate mixture. The results showed that hepatocytes from rats thus identified as obesity-prone oxidized 44% less palmitate in vitro than did those from obesity-resistant rats. This difference in hepatocyte fatty acid oxidation is consistent with and may explain at least in part the reduced capacity of obesity-prone rats to oxidize fat. Keywords: diet-induced obesity; liver; hepatocyte fatty acid oxidation; obesity prone; obesity resistant Consumption of energy-dense diets rich in fat and carbohydrate is thought to be an important contributing cause of obesity, but the mechanisms that underlie such diet-induced obesity are poorly understood. The wide variation in weight gain associated with consumption of high-fat diets both between rats of different strains 1,2 and among rats within a strain 3,4 indicates that preexisting, genetically determined factors underlie susceptibility to diet-induced obesity. Recent studies suggest that a reduced capacity for fat oxidation contributes significantly to the propensity for diet-induced obesity in Sprague-Dawley rats. The in vivo oxidation rate of an intragastric fat load in outbred rats eating a low-fat diet is predictive of subsequent weight gain after rats are fed a highfat food. 5 Pharmacological stimulation of fatty acid oxidation reverses diet-induced obesity. 6 Sprague-Dawley rats selectively bred for susceptibility to diet-induced obesity 4 (Levin rats) and maintained on a low-fat diet also oxidize a fat load more slowly than do those bred for resistance to diet-induced obesity. 7 These inbred obesity-prone (OP) rats also have lower fasting plasma ketone bodies and reduced RNA expression for enzymes involved in hepatic fatty acid uptake and oxidation, 7 suggesting that the limited capacity for fat oxidation in OP rats is due at least in part to limited fatty acid oxidation in the liver. To determine more directly whether hepatic fatty acid oxidation is lower in OP rats than it is in obesity-resistant (OR) animals, we measured the rate of fatty acid oxidation in hepatocytes isolated from these two types of rats. In order to avoid confounding differences in food intake, weight gain and metabolism resulting from consumption of a high-fat diet, we studied hepat...

show abstract

Sympathetic Activity, Age, Sucrose Preference, and Diet‐Induced Obesity

Cited by 38 publications

References 15 publications

Chronic intracerebroventricular injection of TLQP-21 prevents high fat diet induced weight gain in fast weight-gaining mice

Chronic intracerebroventricular injection of TLQP-21 prevents high fat diet induced weight gain in fast weight-gaining mice

Glucokinase Is the Likely Mediator of Glucosensing in Both Glucose-Excited and Glucose-Inhibited Central Neurons

Reduced hepatocyte fatty acid oxidation in outbred rats prescreened for susceptibility to diet-induced obesity

Contact Info

Product

Resources

About