Diet-induced Obesity-resistant Rats Research Articles

N-acetylcysteine reduces addiction-like behaviour towards high-fat high-sugar food in diet-induced obese rats.

Compulsive forms of eating displayed by some obese individuals share similarities with compulsive drug-taking behaviour, a hallmark feature of substance use disorder. This raises the possibility that drug addiction treatments may show utility in the treatment of compulsive overeating. N-Acetylcysteine (NAC) is a cysteine pro-drug which has experienced some success in clinical trials, reducing cocaine, marijuana and cigarette use, as well as compulsive behaviours such as gambling and trichotillomania. We assessed the impact of NAC on addiction-like behaviour towards highly palatable food in a rat model of diet-induced obesity. Adult male Sprague-Dawley rats were placed on a high-fat high-sugar diet for 8weeks and then assigned to diet-induced obesity-prone (DIO) or diet-induced obesity-resistant (DR) groups based on weight gain. DIO and DR rats were subjected to an operant conditioning paradigm whereby rats could lever press for high-fat high-sugar food pellets. This alternated with periods of signalled reward unavailability. Before treatment DIO rats ate more in their home cage, earned more food pellets in operant sessions, and responded more during periods that signalled reward unavailability (suggestive of compulsive-like food seeking) compared with DR rats. This persistent responding in the absence of reward displayed by DIO rats was ameliorated by daily injections of NAC (100mg/kg, i.p.) for 14days. By the end of the treatment period, lever-pressing by NAC-treated DIO rats resembled that of DR rats. These findings suggest that NAC reduces addiction-like behaviour towards food in rats and supports the potential use of this compound in compulsive overeating.

Orexin-A and endocannabinoid signaling regulate glucose-responsive arcuate nucleus neurons and feeding behavior in obese rats

Obesity is a global public health problem. Orexin and endocannabinoid signaling in the hypothalamus have been shown to regulate feeding and are promising molecular targets for obesity treatment. In this study, we attempted to analyze effects of orexin-A and endocannabinoid signaling modulation in the arcuate nucleus (Arc) on feeding and glucose-responsive (GR) neurons physiology in a diet-induced obesity (DIO) and diet-induced obesity resistant (DR) rat model. Administration of orexin-A or cannabinoid receptor type-1 (CB1R) antagonist AM251 altered the firing of GR neurons in the Arc. The effects of orexin-A were eliminated by pre-administrating orexin-1 receptor (OX-1R) antagonist SB334867, respectively. Behavioral studies showed that orexin-A increased food intake, while AM251 reduced feeding. Histological studies showed that mRNA and protein expression of OX-1R (orexin-1 receptor) and CB1R were increased in the Arc of DIO and DR rats. Our results strongly suggest that orexin-A and endocannabinoid signaling in Arc plays an important role in regulating GR neuronal excitability and food intake in obesity.

Effect of Maternal Obesity on Fetal Growth and Expression of Placental Fatty Acid Transporters.

Objective:To explore the effects of maternal high-fat (HF) diet-induced obesity on fetal growth and the expression of placental nutrient transporters.Methods:Maternal obesity was established in rats by 8 weeks of pre-pregnancy fed HF diet, while rats in the control group were fed normal (CON) diet. Diet-induced obesity (DIO) rats and diet-induced obesity-resistant (DIR) rats were selected according to body weight gain over this period. After copulation, the CON rats were divided into two groups: switched to HF diet (CON-HF group) or maintained on the CON diet (CON-CON group). The DIO rats and DIR rats were maintained on the HF diet throughout pregnancy. Pregnant rats were euthanized at day 21 gestation, fetal and placental weights were recorded, and placental tissue was collected. Reverse transcription-polymerase chain reaction was used to determine mRNA expression of placental nutrient transporters. Protein expression was determined by Western blot.Results:Average fetal weight of DIO dams was reduced by 6.9%, and the placentas of CON-HF and DIO dams were significantly heavier than the placentas of CON-CON and DIR dams at day 21 of gestation (p<0.05). The fetal/placental weight ratio of DIO dams was significantly reduced compared with the fetal/placental weight ratio of CON-CON dams (p<0.05). The mRNA expression of GLUT-1 and SNAT-2 were not significantly different between groups. The mRNA and protein expression levels of CD36, FATP-1, and FATP-4 in DIO dams were decreased significantly (p<0.05).Conclusion:Maternal obesity induced by a HF diet led to intrauterine growth retardation and down-regulated the expression of placental fatty acid transporters.

Regulation of hypothalamic neuropeptides gene expression in diet induced obesity resistant rats: possible targets for obesity prediction?

Several factors play a role in obesity (i.e., behavior, environment, and genetics) and epigenetic regulation of gene expression has emerged as a potential contributor in the susceptibility and development of obesity. To investigate the individual sensitivity to weight gain/resistance, we here studied gene transcription regulation of several hypothalamic neuropeptides involved in the control of energy balance in rats developing obesity (diet-induced obesity, DIO) or not (diet resistant, DR), when fed with a high fat diet. Rats have been followed up to 21 weeks of high fat diet exposure. After 5 weeks high fat diet exposure, the obese phenotype was developed and we observed a selective down-regulation of the orexigenic neuropeptide Y (NPY) and peroxisome proliferator-activated receptor gamma (PPAR-γ) genes. No changes were observed in the expression of the agouti-related protein (AgRP), as well as for all the anorexigenic genes under study. After long-term high fat diet exposure (21 weeks), NPY and PPAR-γ, as well as most of the genes under study, resulted not be different between DIO and DR, whereas a lower expression of the anorexigenic pro-opio-melanocortin (POMC) gene was observed in DIO rats when compared to DR rats. Moreover we observed that changes in NPY and POMC mRNA were inversely correlated with gene promoters DNA methylation. Our findings suggest that selective alterations in hypothalamic peptide genes regulation could contribute to the development of overweight in rats and that environmental factor, as in this animal model, might be partially responsible of these changes via epigenetic mechanism.

A comparative study of diet-induced obesity and diet-induced obesity-resistant non-alcoholic fatty liver in rats

Objective To observe the changes of non-alcoholic fatty liver related indices in diet-induced obesity-resistant rats and diet-induced obesity rats. Methods A total of 140 male Sprague Dawley( SD) rats were randomly divided into normal control group ( n = 20,normal diet for 8 weeks) and model group ( n = 120,high fat diet for 8 weeks). The rats of model group were further divided into 2 groups:O -N ( obesity with non-alcoholic fatty liver) and OR-N ( obesity-resistance with non-alcoholic fatty liver) groups. The rats with body mass higher than mean + 1. 96 folds standard deviation were included in O-N group and those with body mass lower than mean + 1. 0 fold standard deviation were included in OR-N group. The animals with the top 20 weight gains in the O-N group and those with the least 20 weight gains in OR-N group were used in the present study. The general conditions and weight changes of rats were dynamically observed for 8 weeks. Eight rats were sacrificed in each group at the end of the 8th week and the following indices were compared among the three groups,including serum levels of alanine aminotransferase ( ALT) ,total cholesterol ( TC) ,triglyceride( TG) ,high-density lipoprotein ( HDL) ,insulin sensitivity index( ISI) ,leptin,energy utilization and body fat ratio. The pathological changes of liver tissues were observed by H-E staining. Results The weight difference of rats in the O-N group and the OR-N group gradually increased; at the end of the 8th week,the weight of rats in O-N group was significantly higher than those in the OR -N group and the normal control group( P 0. 01). The serum levels of ALT,TG,and leptin were significantly increased in both O-N and OR -N groups ( P 0. 05,P 0. 01). The TC,TG,leptin levels and energy utilization in O-N group were significantly higher than those in OR -N group ( P 0. 05,P 0. 01). The HDL and ISI levels in the O-N group were significantly lower than those in the OR-N and normal control groups ( P 0. 01,P 0. 05). Light microscopy showed a great number of fat vacuoles in the liver cells of O-N and OR-N groups. Conclusion High fat diets can induce SD rat to develop non-alcoholic fatty liver with obesity and obesity-resistance. Increase in serum leptin and ISI may play a role in resisting diet-induced obesity and non-alcoholic fatty liver of rats.

Increased expression of receptors for orexigenic factors in nodose ganglion of diet-induced obese rats

The vagal afferent pathway is important in short-term regulation of food intake, and decreased activation of this neural pathway with long-term ingestion of a high-fat diet may contribute to hyperphagic weight gain. We tested the hypothesis that expression of genes encoding receptors for orexigenic factors in vagal afferent neurons are increased by long-term ingestion of a high-fat diet, thus supporting orexigenic signals from the gut. Obesity-prone (DIO-P) rats fed a high-fat diet showed increased body weight and hyperleptinemia compared with low-fat diet-fed controls and high-fat diet-induced obesity-resistant (DIO-R) rats. Expression of the type I cannabinoid receptor and growth hormone secretagogue receptor 1a in the nodose ganglia was increased in DIO-P compared with low-fat diet-fed controls or DIO-R rats. Shifts in the balance between orexigenic and anorexigenic signals within the vagal afferent pathway may influence food intake and body weight gain induced by high fat diets.

The study on mechanism of appetite regulation in diet-induced obesity resistant rats

To explore the cause of decreasing intake food of diet-induced obesity resistant (DIO-R) rats. Fifty male Sprague-dawley (SD) rats were randomly divided into control group and high-fat group and they were fed with basic diet and high-fat diet respectively for 13 weeks. DIO-R and diet-induced obesity (DIO) rats were selected according to their body weight and the quantity of energy intake, then observing the changes of the total food intake, the level of serum leptin and plasma NPY were determined by radioimmunoassay and the contents of the melanocortin receptor-4 (MCR-4) in brain were determined by Western Blot. The total food intake of DIO-R rats was (1 679.1 +/- 146.8) g. The total food intake of DIO rats was (1 818.4 +/- 148.9) g. The total food intake of DIO-R rats was lower than that of DIO rats (P < 0.05). The level of plasma NPY of DIO-R rats was (795.24 +/- 83.59) ng/L. The level of plasma NPY of DIO rats was (1 007.14 +/- 172.83) ng/L. The level of plasma NPY of DIO-R rats was lower than that of the DIO rats (P < 0.05). The levels of serum leptin of basic, DIO-R and DIO rats was (4.80 +/- 0.75) microg/L, (9.17 +/- 1.19) microg/L and (9.32 +/- 1.04) microg/L. The level of serum leptin of rats in high-fat diet group was increased as compared with the rats in basic diet group, but there was no significant difference between DIO-R and DIO rats (P > 0.05). The levels of brain MCR-4 of basic, DIO-R and DIO rats were (342 +/- 31) mm2, (455 +/- 33) mm2, (355 +/- 30) mm2. High fat diets increased the content of brain MCR-4 in DIO-R rats. DIO-R rats decreased appetite by increasing expression of ob gene to reduce activity of NPY pathway and activate the MCR-4 pathway, and thus inhibit the increase body of weight.

Expression of hormone-sensitive lipase mRNA in diet-induced obesity resistant rats

In order to explore the expression of hormone-sensitive lipase (HSL) mRNA in white adipose tissue of diet-induced obesity-resistant (DIO-R) rats. Fifty male Sprague-dawley (SD) rats were randomly divided into control group and high-fat group and they were fed with basic diet and high-fat diet respectively for 13 weeks. DIO-R and DIO rats were selected according to their body weight and the quantity of energy intake, then observing changing of the body fat content, the level of serum growth hormone was determined by radioimmunoassay and the level of the HSL mRNA in white adipose tissue was determined by RT-PCR. The body fat content of DIO-R rats were lower than those of DIO rats (P < 0.05). The level of serum growth hormone of DIO-R rats were higher than those of DIO rats (P < 0.05). High fat diets increased the level of the HSL mRNA in DIO-R rats. Increasing expression of HSL in white adipose tissue may play a part of role in resisting diet-induced obesity of rats.