Increase of adiponectin receptor gene expression by physical exercise in soleus muscle of obese Zucker rats

Aerobic exercise, including treadmill running has been widely used to treat insulin resistance and type 2 diabetes. We studied the effects of endurance training on gene expression of adiponectin receptor 1 (AdipoR1) in skeletal muscle of obese Zucker rats: the 8-week moderate exercise program consisted of treadmill running at 20 m/min and 0° gradient for 1 h/day, 7 days/week. After 8 weeks, insulin action on glucose disposal rate was measured by glucose–insulin index, the product of the areas under the curve of glucose and insulin during intraperitoneal glucose tolerance testing. In contrast to results for sedentary obese rats, exercise training decreased plasma levels of insulin and glucose as well as the glucose–insulin index in obese rats, indicating the merit of regular moderate exercise for improvement of insulin sensitivity in this insulin-resistant animal model. Also, diabetes-related reductions in mRNA and protein content of AdipoR1 in soleus muscle were observed in obese rats at baseline; they were markedly reversed after the 8-week exercise program. However, such exercise training did not alter plasma levels of insulin and glucose in lean Zucker rats. Also, AdipoR1 gene expression in soleus muscle was not changed by exercise in lean Zucker rats compared with the sedentary, lean littermates. These results suggest that long-term exercise training may reverse reduced AdipoR1 gene expression in soleus muscle and improve insulin sensitivity in the obese Zucker rats. Thus, an endurance exercise training is probably helpful clinically for obese individuals with insulin resistance.     

Sympathoadrenal function in genetically obese Zucker rats.

The effects of genetic obesity on the actions and alterations of the sympathetic nervous system were studied in 10-12-month-old obese (fa/fa) and lean (Fa/-) Zucker rats. Blood glucose, plasma insulin, epinephrine (E), norepinephrine (NE), and free fatty acids (FFA) concentrations were measured in blood samples taken through a permanent heart catheter before, during, and after exercise or intravenous infusion of E and NE. Baseline plasma FFA and insulin levels were markedly increased in the obese animals. Exercise, i.e., strenuous swimming against a counter current for 15 min, led to reduction of plasma insulin concentrations and an increase of all other blood components in lean Zucker rats. In obese animals, an exaggerated increase of blood glucose and a large suppression of plasma insulin occurred. Plasma FFA levels tended to decline during exercise. Plasma catecholamine patterns in the exercising fatty Zuckers were not different to those of the lean animals. Infusion of E caused an increase of blood glucose and a decrease of plasma insulin concentrations in both groups of animals. The increase in blood glucose in the obese animals was significantly larger compared to the changes in the lean animals. Infusion of NE significantly reduced plasma insulin concentration in obese but not in lean animals. The results revealed that activation of the sympathetic system, expressed as exercise-induced alterations in plasma E and NE levels, is normal in obese Zucker rats. However, postsynaptic receptor effects of catecholamines on glycogenolysis and lipolysis are different in obese and lean animals, which points to permanent changes in adrenoceptor mechanisms on adipocytes, hepatocytes, and muscle cells in obesity.     

Serum insulin,glucose and triglyceride responses of Zucker obese and lean rats to cholecystokinin

Zucker obese rats are less sensitive to cholecystokinin (CCK), a putative satiety agent which also stimulates insulin and glucagon release. Changes in serum insulin, glucose and triglycerides, which are elevated in the obese rat, were compared with those in lean rats after saline and CCK-8 injection in fed and non-fed rats. Serum insulin increased 15 min after injection of CCK-8 in both lean and obese rats. In lean rats only, insulin subsequently decreased in both fed and non-fed rats. In both lean and obese rats injected with CCK-8 serum glucose did not change with feeding and was less than in saline-injected rats. While triglyceride concentrations were unaffected by either treatment in lean rats, in obese rats they were increased 100% 15 min after injection of CCK-8 and subsequently decreased in both fed and non-fed rats. Thus, CCK-8 elicited changes which were different from those which occur during normal feeding. Increased serum insulin, glucose and triglycerides which occurred 15 min after injection of saline only in obese rats may be due to increased susceptibility to the stress of being injected and may account for the decreased satiety effect of CCK-8.     

Insulin stimulates inositol incorporation in hippocampus of lean but not obese Zucker rats

We have previously reported that intraventricular insulin is ineffective in decreasing the body weight of obese (fa/fa) Zucker rats. In the present study, we report that insulin at concentrations of 1 and 5 nM significantly stimulates incorporation of 3H-myoinositol into inositol phosphates (29 +/- 5% and 20 +/- 6% stimulation over control levels) and membrane inositol lipids (29 +/- 4% and 20 +/- 6% stimulation over control levels) within hippocampal slices from lean (Fa/Fa) Zucker rats (n = 3 preparations). Smaller but significant stimulations were observed in the Fa/fa Zucker rat (n = 5) hippocampus [10 +/- 3 and 13 +/- 4% stimulation over control levels (inositol phosphates) and 10 +/- 4 and 14 +/- 3% stimulation over control levels (inositol lipids) with 1 and 5 nM insulin]. Insulin had no effect on 3H-inositol incorporation into hippocampal slices from obese (fa/fa) Zucker rats (n = 5). No difference in insulin binding to hippocampal membranes was observed among the three genotypes. These findings confirm the behavioral observation of insulin insensitivity within the fa/fa Zucker CNS and suggest that this insensitivity may be gene-dose-related.     

Hyperinsulinemia of preobese and obese fa/fa rats is partly vagus nerve mediated

In vivo glucose-induced insulin secretion was greater in preweaned preobese 17-day-old Zucker rats than in the corresponding controls. This hypersecretion of insulin was reversed to normal by acute pretreatment with atropine. A short-lived (30 s) electrical stimulation of the vagus nerve preceding a glucose load potentiated the in vivo glucose-induced insulin release in adult animals (6-9 wk) and more so in obese Zucker (fa/fa) than in lean rats. This suggested the existence of enhanced sensitivity and/or responsiveness of the B cells of obese animals to the parasympathetic system. That the parasympathetic tone was increased in adult obese Zucker (fa/fa) rats was corroborated by the observation that acute vagotomy of these animals resulted in a significant decrease in glucose-induced insulin secretion, whereas no such effect was seen in lean rats. Also, perfused pancreases from adult obese (fa/fa) rats oversecreted insulin during a stimulation by arginine when compared with controls, an oversecretion that was restored toward normal by superimposed infusion of atropine. It is concluded that a) the increased insulin secretion of preobese Zucker fa/fa rats is an early abnormality that is mediated by the vagus nerve, and b) increased secretion of insulin in adult obese fa/fa rats continues to be partly vagus-nerve mediated, although a decreased sympathetic tone and other unknown defects could conceivably play a role as well.     

Decreased pancreatic CCK receptor binding and CCK-stimulated amylase release in Zucker obese rats

In Zucker obese rats the response to the effects of CCK on food intake and pancreatic exocrine function are decreased. However, it is unknown whether the decreased responsiveness is due to decreased receptor number and/or sensitivity or abnormal circulating concentrations of CCK. In these experiments percent total binding of 125I-CCK-33 to pancreatic acini from obese rats was one-half that in lean rats when data was expressed on a per microgram DNA basis (19.6 +/- 5.1 vs. 47.4 +/- 11.4, p less than 0.01). In a second experiment while the maximally effective dose of CCK for stimulating amylase secretion from dispersed pancreatic acini was similar in obese and lean rats (10(-10) M), less amylase was secreted in obese rats across the dose range tested (p less than 0.001). In contrast, carbachol had similar potency and efficacy in stimulating amylase release from obese and lean pancreatic acini. The increase of pancreas size by use of a trypsin inhibitor was greater in lean than obese rats (p less than 0.03). In addition, stimulation of amylase release by CCK from obese trypsin inhibitor-treated compared with control obese rats was greater than that from lean trypsin inhibitor-treated compared with control lean rats (p less than 0.002). However, overall, stimulation of amylase secretion by CCK was only 36% of control (p less than 0.001) and by carbachol was only 20% of control (p less than 0.001). Thus, increased size by increased cell number was associated with decreased response per cell.(ABSTRACT TRUNCATED AT 250 WORDS)     

Changes in the islets of langerhans in the obese Zucker rat.

Pancreatic islet tissue from lean and obese Zucker rats was investigated with histologic and immunocytochemical techniques, and the changes in cytologic composition were correlated with levels of serum glucose, lipids, and insulin. The insular changes in obese rats progressed in severity with increasing age. Changes consisted of pronounced insulin cell hyperplasia, disarrangement of islet architecture, and disappearance (degranulation?) of a new islet cell type, the pancreatic polypeptide cell. High levels of free fatty acids, triglyceride, and insulin were detected in serum of obese rats. Upon diet restriction, these parameters decreased and islet morphology became normalized. When obese Zucker rats were treated with streptozotocin, high levels of serum free fatty acids and triglycerides remained but there was a great reduction in serum insulin levels to near normal levels. Pancreatic polypeptide cells werenot found in the islets. It is suggested that high free fatty acid and triglyceride levels in obese rats may be related to the inability to demonstrate pancreatic polypeptide cells in the islets of 100- to 300-day-old obese Zucker rats.     

Sensitivity to satiating and taste qualities of glucose in obese Zucker rats

A general "glucoreceptor" defect, demonstrable in pancreatic islet and taste cells, may contribute to the metabolic and taste abnormalities of adult onset diabetes and possibly, if present at the level of the hypothalamus, could produce hyperphagia and the obesity seen in diabetics. To determine if a glucoreceptor defect generally accompanies obesity and glucose intolerance, behavioral responsiveness to glucose was examined in nine obese and nine lean female Zucker rats. Daily food and fluid intake were measured during three two-bottle preference tests, in which rats chose between water and one of several glucose solutions (1%, 3%, and 12%). Taste responsiveness to glucose of obese rats appeared normal; however, increased satiating effects of glucose were found in obese rats, possibly due to an enhanced delivery of glucose to neurons that inhibit feeding, caused by glucose intolerance. Also, obese rats had (a) increased brain weights, and (b) increased volumes of ventromedial and paraventricular hypothalamic nuclei. These findings, perhaps explainable by an increased delivery of nutrients to the developing brain, indicate that the hyperphagia of Zucker rats is due neither to an overt hypothalamic lesion nor to insensitivity to glucose.     

Nociception and opioid-induced analgesia in lean (Fa/-) and obese (fa/fa) Zucker rats

Previous research indicates a possible interrelationship between the endogenous opioids (EO), nociception and food-intake. We therefore considered the hyperphagic obese Zucker rat a good candidate for abnormal responses to nociceptive stimuli. Pairs of lean and obese sisters were tested for latency of response to nociceptive stimuli by tail-flick and tail-pinch methods. Obese rats exhibited shorter latencies in each test, (tail-flick, p less than 0.05 and tail-pinch, p less than 0.001). Dose/response curves for morphine analgesia indicate that morphine is less potent in obese than in lean rats (ED50's = 4.87 +/- 0.62 mg/kg and 3.12 +/- 0.41 mg/kg respectively, p less than 0.05). These data suggest a defect in the EO systems of obese Zucker rats.     

Abnormal brown adipose composition and beta-adrenoceptor binding in obese Zucker rats

The composition, morphology, beta-adrenergic receptor binding, and in vitro lipolysis were examined in lean and obese, 5- to 6-mo-old male Zucker rat interscapular brown adipose tissue (IBAT). IBAT pads from obese rats were heavier (283%), had more lipid (700%), and more (75%)( and larger (83%) adipocytes than those from lean rats. Also, IBAT from obese rats had no multiloculated cells, and 50% of their IBAT adipocytes were the size of white fat cells. High affinity binding for (-)-[3H]dihydroalprenolol (KD, 15-18 nM), as well as the estimated KD values for binding and the 1/2 Vmax values for adrenergic agonist-induced lipolysis were similar in isolated IBAT cells from lean and obese rats. However, adipocytes from IBAT in obese rats had 75% fewer high affinity beta-adrenergic binding sites per cell (Bmax) compared to those in lean rats. These findings are most compatible with the infiltration of IBAT by white adipocytes. Such infiltration would be expected to reduce the overall thermogenic capacity of IBAT in obese Zucker rats and thereby contribute to the maintenance of their obesity.     

Obesity augments the age-induced increase in mitochondrial capacity for H2O2 release in Zucker fatty rats

Aim: Mitochondrial dysfunction has been suggested to play a significant role in obesity and insulin resistance. The aim of the present study was to investigate if changes in obesity and insulin resistance were related to similar changes in mitochondrial capacity for hydrogenperoxide release in Zucker diabetic fatty rats and their lean littermates. Methods: Thirty‐four rats were used in this study. Rats were either lean or obese Zucker rats killed at 5–6 (young) or 12–14 (adults) weeks of age. Mitochondria were isolated from soleus muscles; respiration and release of hydrogenperoxide were determined and related to citrate synthase activity to determine intrinsic mitochondrial function. Mitochondrial‐specific super‐oxide dismuthase (MnSOD) protein content was determined in isolated mitochondria and muscle homogenate. Catalase protein content was determined in muscle homogenate. Results: Young lean and obese rats had a higher mitochondrial respiration when using palmitoyl‐l ‐carnitine as substrate compared with adult lean and obese rats. The obese strain had higher mitochondrial hydrogenperoxide release but only in the adult animals. In both lean and obese animals, increased age was associated with increased mitochondrial hydrogenperoxide release. MnSOD tended to be higher in the obese strain in the isolated mitochondria. Regardless of age, catalase protein content was significantly lower in the obese rats. Conclusions: This study shows that the augmented increase in obesity and insulin resistance seen in Zucker diabetic fatty rats is associated with increased capacity for mitochondrial hydrogenperoxide release.     

Decreased binding to hypothalamic insulin receptors in young genetically obese rats

[125I]insulin binding to partially purified hypothalamic membranes is reduced during prolonged starvation, and changes in hypothalamic insulin binding capacity correlate well with spontaneous variations in energy balance in ground squirrels. To determine whether an insulin binding impairment in the central nervous system can be observed during the early expression of genetic obesity, both obese (fa/fa) and phenotypically lean (Fal-) Zucker rats were studied at 6 weeks of age. Hypothalamic tissue from fa/fa rats bound significantly less hormone than that from the lean animals, but binding was not changed in tissue from cerebral cortex. It is concluded that a defect in insulin binding to hypothalamic receptors in Zucker fatty rats may contribute to the development of weight gain in these animals.     

Impaired neural regulation of insulin secretion related to the leptin receptor gene mutation in Wistar fatty rats

The Wistar fatty (WF) rat is a model of obese Type 2 diabetes mellitus (DM). These rats were bred by crossing Zucker fatty (ZF) and Wistar–Kyoto (WKY) rats. A homo-allelic leptin receptor gene mutation has been reported in ZF rats. We report here how these genetic factors contribute to plasma insulin regulation. The fasting plasma insulin levels were higher in WKY and Wistar lean (WL) rats than in Zucker lean (ZL) rats (p<0.05). The levels in WF and ZF rats were higher than in their respective lean littermates, WL and ZL rats (p<0.05). After intragastric glucose load, the plasma insulin increase was reduced upon pretreatment by intracerebroventricular (i.c.v.) methylatropine (an antagonist of the cholinergic receptor) injection in WL rats (p<0.05) but not in WF rats. Plasma glucagon-like peptide-1 (GLP-1) response to intragastric glucose load was not affected by methylatropine. After selective hepatic-vagotomy, plasma insulin levels increased in wild-type ZL rats (p<0.05). This increase was not observed in heterozygote ZL rats. Surprisingly, this response of plasma insulin was not shown in wild-type WL and WKY rats. ZF and WF rats did show a prominent decrease in insulin response (p<0.05). These results indicate that the genetic factor in ZF rats is associated with impaired vagal nerve-mediated control of insulin secretion. The genetic factor in WKY rats may diminish sensitivity to the vagal information of insulin release and contribute to insulin resistance. Therefore, we conclude that the presence of both genetic factors in a homo-allelic state is important to the development of DM in WF rats.     

Increased sensitivity of Zucker obese rats to naloxone is present at weaning

Increased pituitary and plasma concentrations of opioid peptides in genetically obese rodents may be a cause or consequence of obesity. It has been shown that food intake is decreased more in adult genetically obese rats and mice than lean rats and mice by administration of naloxone, an opiate antagonist. Evidence for an opiate-mediated component in the development of rather than the consequence of obesity would be provided if young, not yet obese, genetically obese rats were more sensitive than lean rats to naloxone. In the present experiment two groups of male and female obese and lean Zucker rats, fasted for 2 hr before the onset of the dark portion of the 12-hr light-dark cycle, were administered 0.125 to 0.5 mg/kg naloxone or 0.5 to 2.0 mg/kg naloxone subcutaneously and 30- and 60-min food intakes were measured. In the group administered the lower doses of naloxone, obese rats of the three ages tested responded more than the lean rats after 30 min (70 vs. 79% of control, p less than 0.02). However, increased sensitivity occurred during the 0-60 min period in rats 4-5 weeks old and 0-30 min period in rats 8-9 and 12-13 weeks old. In the second group tested with the higher doses, the obese responded less than the lean rats (73 vs. 66% of control, p less than 0.05) and there was no difference in response after 0-60 min (66 vs. 61% of control, NS). Thus, increased sensitivity to threshold doses of naloxone occurs before the development of substantial obesity and therefore opiate peptides may play a causal role in obesity.     

Influence of nalmefene on energy balance and glucose regulation in Zucker rats

It has been hypothesized that opioid peptides play a role in the development of obesity. The opiate antagonist naltrexone decreases glucose-stimulated insulin release, while the sensitivity of diabetic rats to naloxone-induced satiety is increased. These findings suggest a possible interaction between glucose concentrations and opiate antagonists in the control of food intake. In three experiments the energy balance and glucose regulatory responses of Zucker obese and lean rats to chronic administration of nalmefene, an opiate antagonist, were measured. Nalmefene, when injected subcutaneously or added to feed for 21 days, decreased food intake and weight gain of obese and lean rats. These responses were more pronounced during the first week of treatment and were greater in obese than lean rats. Nalmefene increased glucose concentrations during day 1 and weeks 1, 2 and 3 only when given subcutaneously. Nalmefene given intragestrically attenuated glucose-stimulated increases in insulin release only in obese rats. Thus, chronic nalmefene administration is not likely to be an effective treatment for obesity or diabetes.     

Satiety in the obese Zucker rat: effects of carbohydrate type and acarbose (Bay g 5421)

Despite the obese Zucker rat's hyperphagia on carbohydrate diets such as laboratory chow, this laboratory has found that its satiety response to glucose and other simple sugars is comparable to that of its lean control rat. To further investigate carbohydrate satiety in the Zucker rat, the short-term feeding behavior of obese and lean rats was observed following intragastric infusions (7.2 kcal in 10 ml) of corn starch and the starch hydrolysates Polycose and dextrin. There were no reliable between-genotype differences in the feeding inhibitory effects of Polycose and dextrin. However, in obese rats, the satiety effect of corn starch was delayed and reduced compared to that observed in lean rats (p less than 0.04). To modify the effect of corn starch, rats were administered 0.2 or 0.6 mg/infusion of the carbohydrate digestive inhibitor acarbose (Bay g 5421). Acarbose significantly reduced the satiety effect of corn starch in lean rats (p less than 0.001), and further attenuated satiety in obese rats (p less than 0.02). Since secretion of pancreatic amylase, the enzyme that initiates starch digestion, is decreased in obese rats, this result suggests that alterations of digestive and/or absorptive processes may underlie the obese rat's impaired satiety response to complex carbohydrate.     

Chronic infusion of the amylin antagonist AC 187 increases feeding in Zucker fa/fa rats but not in lean controls

Numerous studies have established the pancreatic B-cell hormone amylin as an important anorectic peptide affecting meal-ending satiety. In the present study, we investigated the effect of a chronic infusion of the amylin antagonist AC 187 on food intake. The studies were performed using obese Zucker fa/fa rats, which are hyperamylinemic but have a defective leptin and insulin signaling system. A chronic intraperitoneal infusion of the amylin antagonist AC 187 (10 microg/kg/h) significantly increased dark phase and total food intake in Zucker but not in lean control rats. During the 8-day infusion experiment, AC 187 had no clear effect on body weight gain in either group. After acute administration, amylin and its agonist salmon calcitonin (sCT) equally reduced food intake in Zucker and lean control rats while cholecystokinin's (CCK) anorectic effect was weaker in the Zucker rats. We provide evidence for amylin being a potential long-term regulator of food intake because AC 187 increased food intake in obese fa/fa rats but not in lean control animals, which have low baseline amylin levels. Amylin may play some role as lipostatic feedback signal similar to leptin and insulin at least when the leptin and insulin feedback signaling systems are deficient. Despite basal hyperamylinemia in the Zucker rats, they do not seem to be less sensitive to the anorectic effects of amylin or its agonist sCT than respective controls. This contrasts with CCK whose anorectic action is reduced in Zucker rats when compared with lean controls.     

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.     

Memory impairment in obese Zucker rats: an investigation of cognitive function in an animal model of insulin resistance and obesity

The genetically obese Zucker rat is a widely investigated model of pathological changes associated with type 2 diabetes. To assess cognitive function, obese and lean Zucker rats were tested on a variable-interval delayed alternation test of learning and memory. There were no group differences in learning the alternation rule or at short intervals, but obese rats were impaired at longer intervals where performance is hippocampus dependent. Plasma membrane association of the insulin sensitive glucose transporter, GLUT4, was reduced in the hippocampus of obese rats in the absence of changes in total GLUT4 and insulin receptor expression. These results parallel those of human studies in pointing to the susceptibility of the hippocampus and related structures to the adverse environment of diabetes mellitus.     

In-Situ Mechanical Characteristics of the Tongue are not Altered in the Obese Zucker Rat

Study Objectives:

Obese Zucker rats have more collapsible isolated upper airways, compared with their lean counterparts. The functional characteristics of the tongue as a potential mechanism for the enhanced upper airway collapsibility in the obese Zucker rat are unknown. This study measured the functional characteristics of the tongue muscle in lean and obese Zucker rats.

Design:

In-situ tongue force (twitch and peak) and fatigability were measured in anesthetized obese and lean Zucker rats.

Setting:

Animal housing facility at the University of Buffalo.

Subjects:

Eight lean and eight obese Zucker rats.

Intervention:

Tongue force and fatigability were measured before, during, and following cocontraction of the tongue protrudor and retractor muscles via direct stimulation of the common hypoglossal nerve.

Measurements and Results:

Obese rats were significantly heavier than their lean counterparts (718 ± 101 gm vs. 545 ± 32, P < 0.05). Total force production at all stimulation frequencies was not different between lean and obese Zucker rats before or after fatigue (P = 0.436). Forces were significantly reduced at the end of the 5-minute stimulation period (P < 0.001) and returned to baseline within 1 minute after fatigue in both lean and obese rats. At the end of the fatigue protocol, tongue force averaged 63.3% ± 13.8% and 72.3% ± 17.8% of the initial force in obese and lean rats respectively (P = 0.85).

Conclusion:

Obesity does not alter the in-situ force production of the tongue muscle. Thus, increases in collapsibility of the isolated upper airway previously noted in obese Zucker rats cannot be ascribed to upper airway muscle dysfunction or enhanced fatigability.

Citation:

Ray AD; Farkas GA; Pendergast DR. In-situ mechanical characteristics of the tongue are not altered in the obese Zucker rat. SLEEP 2009;32(7):957-961.