Hepatic mitochondria in diet-induced obese mice (stereology and molecular analysis) / Mitocondrias hepáticas en ratones obesos inducidos por la dieta (estereología y análisis molecular)

SUMMARY: The world population is going through an obesity epidemic that has severe consequences for the health system. This study focused on studying hepatic mitochondria in obese animals induced by a high-fat (HF) diet and used the model-based stereology in electron micrographs for the quantitative study. Besides, the gene expressions of molecular markers of mitochondrial biogenesis carnitine palmitoyltransferase 1a (Cpt 1α), mitochondrial transcription factor a (Tfam), uncoupling protein 3 (Ucp 3), and nuclear respiratory factor 1 (Nrf 1) were analyzed. The HF diet caused a weight gain of +1820 % comparing the control group (C) with the HF group (from 0.32±0.31 g to 5.5±0.39 g, P<0.001). The HF group showed fat droplets in the hepatocyte cytoplasm (steatosis) and less dense and large mitochondria in transmission electron microscopy. The mitochondria size (cross-section) did not show a significant difference between the groups C and HF. However, the mitochondria numerical density per area was 30 % less, the mitochondrial surface density (outer membrane) was 20 % less, and the mitochondrial volume density was 22 % less in the HF group than the C group. The gene expressions of molecular markers of mitochondrial biogenesis Cpt 1α, Tfam, Ucp 3, and Nrf 1 decreased in the HF group compared to the C group. The quantitative results match perfectly with the molecular ones of mitochondrial biogenesis markers. In the future, it will be crucial to verify if and how these data recover with the reduction of obesity, which would be of significant interest given the current obesity epidemic that affects the world population.

RESUMEN: La población mundial atraviesa una epidemia de obesidad que tiene graves consecuencias para el sistema de salud. Este estudio se centró en el análisis de las mitocondrias hepáticas en animales obesos inducidos por una dieta alta en grasas (HF) y utilizó la estereología basada en modelos en micrografías electrónicas para el estudio cuantitativo. Además, se analizaron las expresiones génicas de los marcadores moleculares de la biogénesis mitocondrial carnitina palmitoiltransferasa 1a (Cpt 1α), factor de transcripción mitocondrial a (Tfam), proteína desacoplante 3 (Ucp 3) y factor respiratorio nuclear 1 (Nrf 1). La dieta HF provocó un aumento de peso de +1820 % comparando el grupo de control (C) con el grupo HF (de 0,32 ± 0,31 g a 5,5 ± 0,39 g, P <0,001). El grupo HF mostró gotas de grasa en el citoplasma de los hepatocitos (esteatosis) y mitocondrias menos densas y grandes en la microscopía electrónica de transmisión. El tamaño de las mitocondrias (sección transversal) no mostró una diferencia significativa entre los grupos C y HF. Sin embargo, la densidad numérica de mitocondrias por área fue 30% menor, la densidad de superficie mitocondrial (membrana externa) fue 20 % menor y la densidad de volumen mitocondrial fue 22 % menor en el grupo HF que en el grupo C. Las expresiones génicas de los marcadores moleculares de la biogénesis mitocondrial Cpt 1α, Tfam, Ucp 3 y Nrf 1 disminuyeron en el grupo HF en comparación con el grupo C. Los resultados cuantitativos coinciden perfectamente con los moleculares de los marcadores de biogénesis mitocondrial. En el futuro, será crucial verificar si estos datos se recuperan y cómo se recuperan con la reducción de la obesidad, lo que sería de gran interés dada la actual epidemia de obesidad que afecta a la población mundial.

Clinical Efficacy of Modified Xiao Chengqitang Combined with Acupoint Catgut Implantation in Treating Diet-induced Obesity Syndrome of Stomach Heat Dampness Obstruction / 中国实验方剂学杂志

Objective:To observe the clinical efficacy and safety of modified Xiao Chengqitang combined with acupoint catgut implantation in treating diet-induced obesity （DIO） syndrome of stomach heat dampness obstruction. Method:One hundred and seventy-two patients were randomly divided into control group（84 cases） and observation group（88 cases）. Both groups of patients received diet and exercise lifestyle adjustments， and acupoint catgut implantation was performed， 10 days for 1 time， 5 days intervals and then catgut implantation again， for a total of 6 times. Patients in observation group took modified Xiao Chengqitang granular powder， 10 g/time， with lukewarm boiled water in morning and evening. Patients in control group took modified Xiao Chengqitang granular powder simulant， 10 g/time， with lukewarm boiled water， 2 times/day. The treatment courses continued 4 months in two groups. Then the body mass index （BMI）， fat percentage （F%）， obesity， waist to hip ratio （WHR） were measured before and after treatment. Color Doppler ultrasonography was used to measure abdominal fat thickness， prehepatic fat thickness （AHF）， perirenal fat thickness （PRF）， and visceral fat index （UVI）. Fasting blood glucose （FBG）， triglyceride （TG）， total cholesterol （TC）， high-density lipoprotein-cholesterol （HDL-C）， low-density lipoprotein-cholesterol （LDL-C）， fasting insulin （FINS）， leptin （LP）， and adiponectin （APN） were detected before and after treatment， and the homeostasis model assessment of insulin resistance （HOMA-IR） index was calculated. In addition， safety evaluation was also conducted. Result:The BMI， F%， obesity degree and WHR in observation group were all lower than those in control group （<italic>P</italic><0.05 or <italic>P</italic><0.01）. Subcutaneous fat thickness， AHF， PRF and UVI in observation group were lower than those in control group （<italic>P</italic><0.01）. The TG， TC， LDL-C and FINS levels in observation group were lower than those in control group （<italic>P</italic><0.01）. The LP and HOMA-IR were also lower than those in control group （<italic>P</italic><0.01）， while the APN was higher than that in control group （<italic>P</italic><0.01）. The total effective rate in clinical application was （71/80） 88.75% in the observation group， higher than （57/75） 76.00% in the control group （<italic>χ</italic>²=4.374，<italic> P</italic><0.05）. Conclusion:Modified Xiao Chengqitang combined with acupoint catgut implantation in treating DIO syndrome of stomach heat dampness obstruction can adjust LP， APN and other factors， improve energy metabolism such as sugar and fat， and effectively control obesity with high safety， so it is worthy of clinical use.

Progress of the mechanism research of acupuncture in treatment of diet-induced obesity / 针刺研究

The literature of experimental research on diet-induced obesity treated with acupuncture was retrieved. The aspects of epigenetics, neuroendocrine system, intestinal flora, inflammatory response, oxidative stress and substance metabolism of the mechanism of acupuncture in the treatment of diet-induced obesity were summarized. It is suggested that the potential mechanism of acupuncture in the treatment of diet-induced obesity should be discussed in the aspects of the interaction of Toll-like receptors on obesity-intestinal flora-immune function, the improvement of insulin resistance, epigenetics and antioxidant stress.

Effect of Lidan Ruanjian Prescription on Lipid-lowering and Antiobesity andMetabolic Profile of Bile Acid / 中国实验方剂学杂志

Objective:To investigate the pharmacodynamics effects of antiobesity, lipid-lowering and the regulations of serum bile acid profiles of Lidan Ruanjian prescription (LDRJ) in obesity rats induced by high-fat diet. Method:The 42 rats were fed high-fat diet for 9 weeks to establish model of obese rats，24 rats were randomly divided into model group, high and low-dose LDRJ group (30,15 g·kg-1). Another 8 normal rats were selected as the normal group.The model group and normal group were given normal saline, and drug group was given the corresponding dose of drug for 4 weeks. Body weight, liver weight, white adipose tissue (WAT) weight were determined after administration medicine for 4 weeks. The bile flow of the rats was measured by bile duct intubation and fasting serum lipid levels of total cholesterol (TC), total triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) were detected by automatic biochemical analyzer. Ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) assay was used to test serum bile acid profile of each group rats. Result:Compared with the control group, the average body weight, liver weight, WAT weight of the model group were significantly increased (P<0.01), while the fasting serum TC, TG and LDL-C levels were elevated (P<0.05，P<0.01). The total bile secretion and bile flow at each test point within 2 h were decreased and the proportion of primary bile acids was decreased (P<0.05).The serum total bile acid content decreased significantly（P<0.01），levels of cholic acid (CA), deoxycholic acid (DCA), chenodeoxycholic acid (CDCA), hyodeoxycholic acid (HDCA), taurocholic acid (TCA), taurodeoxycholic acid (TDCA), taurochenodeoxycholic acid (TCDCA), taurohyodeoxycholic acid (THDCA) and glycodeoxycholic acid (GDCA) were significantly reduced (P<0.05，P<0.01). Compare with model group, body weight, liver weight in high and low-dose LDRJ groups reduced significantly(P<0.05，P<0.01). Fasting serum TC, TG and LDL-C levels were decreased in high-dose group(P<0.05，P<0.01), so did as TG levels in low-dose group(P<0.05). The bile flow rate increased significantly in high-dose group 1~1.5 h after administration (P<0.05). All dose treatment groups increased the proportion of primary bile acids (P<0.05) and changed the bile acid profile, especially elevated the bile acid levels of TCA, DCA, glycocholic acid (GCA), GDCA in high-dose LDRJ group (P<0.05，P<0.01), while TCA and TCDCA in low-dose group (P<0.05). Conclusion:LDRJ has significant lipid-lowering and antiobesity effects and the mechanism might involve the increase of bile secretion, the stimulation of primary bile acid synthesis and the regulation of bile acid profile.

Effects of orexin-A on firing activity of gastric distension-sensitive neurons in the basomedial amygdala and food intake in diet-induced obese rats / 中华行为医学与脑科学杂志

Objective To investigate the effects of orexin-A on firing activity of gastric distensionsensitive (GD) neurons in the basomedial amygdala (BMA) and food intake in diet-indaced obese rats.Methods Healthy male Wistar rats were selected,and the diet-induced obesity (DIO) rat model and dietinduced resistant (DR) rat model were established by high-fat diet.The effects of orexin-A and an opioid receptor antagonist naloxone on BMA GD neurons were observed by recording the extracellular potentials of single neurons.The effects of orexin-A and naloxone on the food intake of different rats were observed by using BMA catheterization.The mRNA expression and protein expression of orexin-1 receptor (OX-1R) and μ opioid receptor were detected by real-time PCR and Elisa,respectively.Results After microinjection of orexinA into the BMA,the firing frequency of GD-sensitive neurons in the normal rats was significantly increased (GD-E:(78.3±6.9)％,GD-Ⅰ:(55.5±4.7) ％,P＜0.01),and this effect was completely blocked by OX-1R receptor antagonist SB334867,and naloxone partially blocked the discharge-promoting effect of orexin-A;Compared with the normal rats,the firing frequency of GD-sensitive neurons in the DIO (GD-E:(91.6±7.1) ％,GD-Ⅰ:(67.9±8.1) ％) and DR(GD-E:(87.9±6.8) ％,GD-Ⅰ:(69.2±5.8) ％) rats was significantly increased after BMA injection of orexin-A (P＜0.05).After administration of orexin-A into the BMA,food intake of the normal rats,DIO rats and DR rats ((2.38±0.34) g,(3.75 ±0.32) g,(4.01 ±0.38) g,respectively) was significantly increased (P＜0.01),and the food intake of DR and DIO rats were significantly higher than that of normal rats (P＜0.05).After BMA was injected with naloxone,the food intake of rats was inhibited,and the food intake of the DIO rats was significantly lower than that of the DR rats (P＜0.05),food intake of the DR rats was significantly lower than that of the normal rats (P＜0.05).The results of real-time PCR showed that the mRNA levels of OX-1R in DIO and DR rats were(5.85±0.45)and (6.03±0.42)were higher than that of normal rats,and the difference was significant (P＜0.05);and mRNA levels of μ-opioid receptors in DIO and DR rats((4.51±0.42) and (8.31±0.41) times) were higher than those in normal rats (P＜0.05).The results of Elisa showed that the protein levels of OX-1R in DIO ((2.98±0.28) ng/μl)and DR rats ((3.05±0.31) ng/μl) were higher than those in normal rats ((1.53±0.31) ng/μl,P＜0.05).The content of μ-opioid receptor protein in DR rats ((4.21±0.35) ng/μl) was higher than that of DIO rats ((2.77±0.27) ng/μl),and higher than that of normal rats((1.48±0.32) ng/μ),the difference was significant (P＜0.05).Conclusion BMA orexin-A promotes the spontaneous discharge of GD-sensitive neurons and food intake in normal rats,DIO rats and DR rats,μ-opioid receptors may be involved in the regulation of this process.

Activation of Local Renin Angiotensin System Induced by TLR4 Signaling Pathway in Adipose Tissues in DIO Mce / 实用医学杂志

Objective To investigate the activation of local renin-angiotensin system induced by TLR4 signaling pathway in the adipose tissues in diet-induced obesity(DIO)mice. Methods C57BL/6 mice,six-week-old,male,were divided randomly into normal-diet group and high-fat diet group. High-fat diet group was fed for 14 weeks. Mice,which weighted up 20%,were divided into 3 groups:obesity-group(OB,n=5),fenofibrate group (FF,n = 5)and TAK242 group(TAK,n = 5). The fenofibrate group was given fenofibrate(100 mg/kg/day)by oral gavage for a further 2 weeks and the TAK242 group TAK-242(3 mg/kg/d)by intraperitoneal injection for 2 weeks. The 23-week-aged mice were sacrificed and the triglyceride(TG),nonesterified fatty acid(NEFA),glutamic-pyruvic transaminase(ALT),aspartate aminotransferase(AST)were measured. NEFA in liver tissues were measured with ELISA and the expression levels of AT1R,AGT and TLR4 were measured by RT-PCR. Results TAK-242(Resatorvid)inhibited the expressions of AT1R,AGT and TLR4 in adipose tissues. The effects of fenofi-brate were different in adipose tissues and liver tissues. Conclusion Activation of TLR4 signaling path way ac-tives the local RAS in adipose tissues. The expressions of AT1R and AGT in adipose tissue are significantly inhibit-ed by TAK-242.

The antioxidant activity of steamed ginger and its protective effects on obesity induced by high-fat diet in C57BL/6J mice

BACKGROUND/OBJECTIVES: Ginger, a root vegetable, is known to have antioxidant and antiobesity effects. Preparation, such as by steaming, can affect the chemical composition of prepared root vegetables or herbs and can change their functional activities. In the present study, we investigated the protective effects of steamed ginger against oxidative stress and steatosis in C57BL/6J mice fed a high-fat diet. MATERIALS/METHODS: The levels of polyphenols and flavonoids in two different extracts of steamed ginger, i.e., water extract (SGW) and ethanolic extract (SGE); as well, their antioxidant activities were examined. Forty male C57BL/6J mice were fed a normal diet (ND, n = 10), high-fat diet (HFD, 60% fat, w/w, n = 10), HFD supplemented with 200 mg/kg of SGE or garcinia (GAR) by weight (SGED or GARD, respectively, n = 10) for 12 weeks. Serum chemistry was examined, and the expressions of genes involved in lipid metabolism were determined in the liver. Histological analysis was performed to identify lipid accumulations in epididymal fat pads and liver. RESULTS: The SGE had higher contents of polyphenols and flavonoids and higher DPPH and ABTS⁺ free radical scavenging activities compared to those of SGW. Treatment with SGE or GAR significantly decreased the HFD-induced weight gain. Both SGE and GAR significantly reduced the high serum total cholesterol (TC), triglyceride (TG) and low-density lipoprotein levels induced by HFD. Compared to ND, HFD significantly increased hepatic TC and TG levels. SGE or GAR supplementation significantly decreased the increase of hepatic lipids by HFD. Interestingly, SGE had a more significant effect in reducing hepatic TC and TG levels than GAR. Furthermore, hepatic genes involved in lipogenesis and lipolysis were altered in both the SGED and GARD groups. CONCLUSIONS: The present study indicates that steamed ginger supplementation can decrease plasma TC and TG and can inhibit liver steatosis by regulating the expressions of hepatic genes.

Effects of intermittent ladder-climbing exercise training on mitochondrial biogenesis and endoplasmic reticulum stress of the cardiac muscle in obese middle-aged rats

The aim of this study is to investigate the effects of intermittent ladder-climbing exercise training on mitochondrial biogenesis and ER stress of the cardiac muscle in high fat diet-induced obese middle-aged rats. We induced obesity over 6 weeks of period in 40 male Sprague-Dawley rats around 50 weeks old, and were randomly divided into four experimental groups: chow, HFD, exercise+HFD, and exercise+chow. The exercising groups underwent high-intensity intermittent training using a ladder-climbing and weight exercise 3 days/week for a total of 8 weeks. High-fat diet and concurrent exercise resulted in no significant reduction in body weight but caused a significant reduction in visceral fat weight (p<0.05). Expression of PPARδ increased in the exercise groups and was significantly increased in the high-fat diet+exercise group (p<0.05). Among the ER stress-related proteins, the expression levels of p-PERK and CHOP, related to cardiac muscle damage, were significantly higher in the cardiac muscle of the high-fat diet group (p<0.05), and were significantly reduced by intermittent ladder-climbing exercise training (p<0.05). Specifically, this reduction was greater when the rats underwent exercise after switching back to the chow diet with a reduced caloric intake. Collectively, these results suggest that the combination of intermittent ladder-climbing exercise training and a reduced caloric intake can decrease the levels of ER stress-related proteins that contribute to cardiac muscle damage in obesity and aging. However, additional validation is required to understand the effects of these changes on mitochondrial biogenesis during exercise.

Effects of Mori Folium extract on diet-induced obesity mechanism in rats / 中国中药杂志

To study the anti-obesity effect of Mori Folium extract on diet-induced obesity(DIO) and to explore the preliminary mechanism in rats. DIO rat models were established by high glucose and high fat diet for 8 weeks. Then high(10 mg•kg⁻¹) and low(5 mg•kg⁻¹) does Mori Folium extracts were given by intragastric administration for 13 weeks. After the last administration, their body weight, 24 h food intake, water intake, Lee's index, liver/body mass index, and fat/body mass index were determined. The levels of lipoprotein lipase(LPL), CCAAT/enhancer-binding protein alpha(C/EBPα) and peroxisome proliferator-activated receptor gamma(PPARγ) were measured by enzyme-linked immunosorbent assay(ELISA). Phosphorylated AMP-activated protein kinase alpha(p-AMPKα), C/EBPα and PPARγ expression levels in adipose tissues were detected by Western blot. The hematoxylin-eosin staining(HE) was used to observe the histopathological changes of adipose tissues. The results showed that both high dose and low dose Mori Folium extract can decrease body weight, Lee's index, renal fat/body mass ratio and testicle fat/body mass ratio, and the high dose group could decrease the total fat/body mass ratio. Both high dose and low dose groups had no significant effect on the food intake and water intake; however, they could decrease levels of LPL in fat, up-regulate p-AMPKα protein expression, down-regulate C/EBPα and PPARγ protein expression, and reduce fat cell volume. In conclusion, Mori Folium extract had a slimming effect on DIO rats, and its mechanism may be associated with up-regulating the expression of p-AMPKα, down-regulating the expression of PPARγ, C/EBPα and LPL, inhibiting the differentiation of preadipocytes into mature fat cells, and reducing the volume of fat cells.

Effects of Electro-acupuncture on Insulin Resistance and Hypothalamic Agouti Gene-related Protein and Neuropeptide Y in Obesity Rats / 中国中医药信息杂志

Objective To observe the effects of electro-acupuncture (EA) on body weight, insulin resistance, hypothalamic agouti gene-related protein (AGRP) and neuropeptide Y (NPY) in diet induced obesity (DIO) rats; To discuss its mechanism for DIO.Methods Fifty SD male rats were randomly divided into low fat diet groups (LFD) and high fat diet group. After the DIO models were established, the successful model rats were randomly divided into model group, EA group and Orlistat (OLST) group. EA was applied to “Zusanli” (ST36) and “Quchi” (LI11) for 20 minutes. The treatment was done once a day for 28 days. OLST was treated with orlistat by gavage. LFD and model did not receive treatment. Body weight was recorded every day. FPG and FINS were detected. The expressions of AGRP and NPY were detected by RT-QPCR. Morphological changes of adipocyte and liver were examined by HE staining.Results The body weight, HOMA-IR, AGRP, NPY and diameter of adipocyte of EA group and OLST group were significantly lower than model group (P<0.05), difference between EA group and OLST group. The states of hepatic steatosis were improved in EA group and OLST group.Conclusion EA has the effects on weight loss by inhibiting the expressions of AGRP and NPY by improving IR.

Rodent Models of Diet-induced Obesity

The prevalence of obesity is rapidly increasing worldwide, and its complications such as type 2 diabetes and cardiovascular disease are also increasing. To avoid long-term damage caused by obesity and its complications, we must develop preventive measures and therapeutic agents based on the pathophysiology of human obesity. However, genetically-modified rodents are mainly used for obesity research. This type of animal model is not very suitable for the study of human obesity because environmental factors such as excessive food intake and sedentary lifestyle are major causes of the recent explosion in human obesity. Therefore, diet-induced obesity rodent models are more appropriate for research in human obesity. Type of diet, animal species, duration of food intake, age, and sex can play a role in determining body weight and levels of glucose, insulin, triglycerides, and leptin. Animal housing conditions such as the number of animals per cage, ambient temperature, and length of the light-dark cycle also influence body weight and metabolic parameters. As a result, many influencing factors should be considered in the development of an appropriate diet-induced obesity rodent model for successful obesity research.

Effects of Difference Chinese Medicinal Herbs for Tonifying Spleen on Obesity Degree and Insulin Resistance in Diet-induced Obesity Rats / 中国中医药信息杂志

Objective To observe the effects of Chinese medicinal herbs with the efficacy of invigorating spleen, upbearing the clear, and tonifying spleen on the obesity degree, fat hormones, and insulin resistance in diet-induced obesity (DIO) rats;To choose better anti-obesity herbs from different Chinese medicinal herbs that can tonify spleen. Methods Among the 130 Wistar rats, 10 were chosen as the blank control group (fed with basal forage), and the remaining 120 were administered with high-fat high-nutrition forage for 13 weeks. According to weight, 50 DIO rats and 10 diet-induced obesity resistance (DIO-R) rats were obtained. DIO rats were divided into model group (normal saline), sibutramine group, invigorating spleen group (Atractylodix Rhizome and Magnoliae Officinalis Cortex), upbearing the clear group (Bupleuri Radix and Aurantii Fructus Immaturus) and medicine for tonifying qi and spleen group (Astragali Radix). All groups received gavage with corresponding drugs. Rats in the blank control group and the DIO-R group received gavage with normal saline. The basal forage was administered to rats in the blank control group, while high-fat forage was continually given to rats in the other six groups. Insulin resistance index (IRI), blood glucose, triglycerides, cholesterol, tumor necrosis factor α (TNF-α) and adiponectin were detected after blood withdrawing. TNF-α and adiponectin in the fat homogenate were examined. Results Compared with the blank control group, body weight, IRI, and cholesterol of rats in the model group significantly increased (P<0.01);adiponectin in homogenate reduced (P<0.01);serum and adipose homogenate TNF-α increased (P<0.01). Compared with model group, body weight, IRI, cholesterol of rats in DIO-R group significantly decreased (P<0.01);adiponectin in fat homogenate increased (P<0.01). Body weight and cholesterol of rats in the sibutramine group significantly decreased (P<0.01), while serum and adipose homogenates TNF-αdecreased (P<0.05, P<0.01). Body weight, IRI and cholesterol of rats in upbearing the clear group decreased (P<0.05, P<0.01);serum and adipose homogenate TNF-α decreased (P<0.05, P<0.01);adiponectin increased in fat homogenate (P<0.05). IRI, cholesterol and serum TNF-αof rats in the invigorating spleen group decreased (P<0.05, P<0.01);adiponectin in serum and adipose homogenate increased (P<0.05). BMI, blood glucose, IRI and cholesterol of rats in Astragali Radix group decreased (P<0.05, P<0.01);TNF-α decreased and adiponectin increased in serum and adipose homogenate (P<0.05, P<0.01). Conclusion Astragali Radix could reduce obesity induced by high-fat forage, and its effects on improving glucose and lipid metabolism disorder and IR are better than the other TCM groups. Its mechanism is related to decreasing TNF-α and increasing adiponectin level.

Anti-adipogenic effect of Artemisia annua in diet-induced-obesity mice model

Obesity has increased continuously in western countries during the last several decades and recently become a problem in developing countries. Currently, anti-obesity drugs originating from natural products are being investigated for their potential to overcome adverse effects associated with chemical drugs. Artemisinic acid, which was isolated from the well-known anti-malaria herb Artemisia annua (AA) L., was recently shown to possess anti-adipogenic effects in vitro. However, the anti-adipogenic effects of AA in animal models have not yet been investigated. Therefore, we conducted daily oral administration with AA water extract in a diet-induced obesity animal model and treated 3T3-L1 cells with AA to confirm the anti-adipogenic effects in the related protein expressions. We then evaluated the physiology, adipose tissue histology and mRNA expressions of many related genes. Inhibition of adipogenesis by the AA water extract was observed in vitro. In the animal model, weight gain was significantly lower in the AA treated group, but there were no changes in food intake volume or calories. Reductions in lipid droplet size and mRNA expression associated with adipogenesis were also observed in animal epididymal fat. This study is the first to report that AA has an anti-obese effects in vivo.

B-cell-activating factor is a regulator of adipokines and a possible mediator between adipocytes and macrophages

3T3-L1 adipocytes express the B-cell-activating factor (BAFF) and three different BAFF receptors (BAFF-Rs). Furthermore, BAFF expression is regulated by inflammatory modulators, such as tumor necrosis factor-alpha and rosiglitazone. Here we investigated the function of BAFF in 3T3-L1 adipocytes and RAW 264.7 macrophages. We examined adipokine expression in 3T3-L1 adipocytes treated with 10 ng ml-1 BAFF. We also examined inflammatory molecule expression in RAW 264.7 macrophages treated with 10 or 100 ng ml-1 BAFF. We examined BAFF expression in the coculture of 3T3-L1 adipocytes and RAW 264.7 macrophages, as well as in white adipose tissue (WAT) of diet-induced obese (DIO) mice. We found that BAFF decreases leptin and adiponectin expression, but increases the expression of proinflammatory adipokines monocyte chemotactic protein-1, interleukin-6 (IL-6), cyclooxygenase-2 (COX-2) and haptoglobin. Coculturing the two cell types resulted in increased BAFF mRNA and protein expression, as well as modulation of BAFF-R mRNA expression in both cell types. These data indicate that BAFF might mediate adipocyte and macrophage interaction. When RAW 264.7 macrophages were treated with BAFF, BAFF-R expression was modulated as in coculture, and nitric oxide synthase and IL-6 expression increased. BAFF expression also increased in WAT of DIO mice. We propose that BAFF can regulate adipokine expression and possibly mediate adipocyte and macrophage interaction.

Antiobesity effect of Safoof Mohazzil, a polyherbal formulation, in cafeteria diet induced obesity in rats.

Obesity is reaching epidemic proportions all over the world yet it lacks adequate treatment. Most of the drugs have failed either due to ineffectiveness or adverse effects. Complementary and alternative system of medicine is being used since ancient times. However, many of them have not been tested for efficacy and safety using modern scientific methods. Therefore, the antiobesity effect of Safoof Mohazzil, a polyherbal formulation, was evaluated in cafeteria diet induced obesity in female Sprague Dawley rats. Animals weighing 100–150 g were divided into four groups (n=8) i.e. standard pellet diet, cafeteria diet control, cafeteria diet + Safoof Mohazzil and standard pellet diet plus Safoof Mohazzil. The formulation was administered orally at a dose of 1 g/kg/day for 14 weeks. At the end of study, cafeteria diet significantly increased body weight, Lee’s index, lipid profile (cholesterol and triglycerides), insulin and leptin levels as compared to standard pellet diet control group. Fourteen week treatment with Safoof Mohazzil significantly prevented the increase in body weight, Lee’s index, lipid profile, insulin and leptin levels as compared to cafeteria diet control group without affecting food and water intake. Safoof Mohazzil had no adverse effect on hepatic transaminases, locomotor activity and motor coordination. The study provides evidence for antiobesity effect of Safoof Mohazzil.

A Hypercaloric pellet-diet cycle induces obesity and co-morbidities in wistar rats / Ciclo de dietas hipercalóricas induz obesidade e comorbidades em ratos wistar

The present study was carried to develop and analyze the consequences of hypercaloric pellet-diet cycle that promotes obesity in rats. Male Wistar rats were randomly distributed into two groups that received either normal diet (ND; n =32; 3,5 Kcal/g) or a hypercaloric diet (HD; n =32; 4,6 Kcal/g). The ND group received commercial Labina rat feeding while the HD animals received a cycle of five hypercaloric diets over a 14-week period. The effects of the diets were analyzed in terms of body weight, body composition, hormone-metabolite levels, systolic arterial pressure and glucose tolerance at the 5 percent significance level. The hypercaloric pellet diet cycle promoted an increase in body weight and fat, systolic arterial pressure and a high serum level of glucose, triacylglycerol, insulin and leptin. The HD group also presented an impaired glucose tolerance. In conclusion, the results of this study show that the hypercaloric pellet-diet cycle promoted obesity in Wistar rats and displayed several characteristics that are commonly associated with human obesity, such as high arterial pressure, insulin resistance, hyperglycaemia, hyperinsulinaemia, hyperleptinaemia and dyslipidaemia.

O objetivo do estudo foi desenvolver um ciclo de dietas hipercalóricas para promover obesidade em ratos. Ratos Wistar foram distribuídos em dois grupos: dieta normal (ND = 32; 3,5 kcal/g) e dietas hipercalóricas (HD; n = 32; 4,6 kcal/g). O grupo ND recebeu ração comercial e os animais HD um ciclo de diferentes dietas hipercalóricas, por 14 semanas. As variáveis analisadas foram peso corporal, parâmetros metabólicos e hormonais, pressão arterial sistólica e teste oral de tolerância à glicose. O nível de significância foi de 5 por cento. O ciclo de dietas hipercalóricas promoveu aumento de peso e gordura corporal, pressão arterial sistólica e níveis séricos de glicose, triacilglicerol, insulina e leptina no grupo HD. Além disso, o grupo HD apresentou tolerância à glicose diminuída. Em conclusão, os resultados deste estudo mostram que o ciclo de dietas hipercalóricas promove obesidade e exibe várias características comumente associadas com a obesidade humana, como aumento da pressão arterial, resistência à insulina, hiperglicemia, hiperinsulinemia, hiperleptinemia e dislipidemia.

Misclassification probability as obese or lean in hypercaloric and normocaloric diet

The aim of the present study was to determine the classification error probabilities, as lean or obese, inhypercaloric diet-induced obesity, which depends on the variable used to characterize animal obesity. Inaddition, the misclassification probabilities in animals submitted to normocaloric diet were also evaluated.Male Wistar rats were randomly distributed into two groups: normal diet (ND; n=31; 3,5 Kcal/g) and hypercaloric diet (HD; n=31; 4,6 Kcal/g). The ND group received commercial Labina rat feed and HDanimals a cycle of five hypercaloric diets for a 14-week period. The variables analysed were body weight, body composition, body weight to length ratio, Lee index, body mass index and misclassification probability. A 5% significance level was used. The hypercaloric pellet-diet cycle promoted increase of body weight, carcass fat, body weight to length ratio and Lee index. The total misclassification probabilities ranged from 19.21% to 40.91%. In conclusion, the results of this experiment show that misclassification probabilities occur when dietary manipulation is used to promote obesity in animals. This misjudgement ranges from 19.49% to 40.52% in hypercaloric diet and 18.94% to 41.30% in normocaloric diet.

Experimental study of diet-induced obesity animal model / 中国药理学通报

AIM To observe the influence of high fat diet on the success rate of diet induced obesity rat. METHODS Rats of model group were fed with hight fat diet for 16 weeks then, the weight and Lee index were measured and compared with those of normal control group. RESULTS The weight and Lee index of model group rats were 491 62?46 89 and 319 04?9 49. Those of the normal control group rats were 394 2?50 78 and 304 63?5 99. There were significant difference between the two groups( P