Fat Pad Weight Research Articles

Anti-obesity and fatty liver-preventing activities of Loniceracaerulea in high-fat diet-fed mice.

Blue honeysuckle (BH, Lonicera caerulea) is used as a traditional medicine in Russia, Japan and China, but is not commonly considered as an edible berry in Europe, USA or Korea. BH has been revealed to decrease serum cholesterol and triacylglycerol (triglyceride or TG) levels through the activation of AMP-activated protein kinase (AMPK), thus it is expected to be a health functional food and pharmaceutical agent for the prevention of non-alcoholic liver damage, in addition to effects as a suppressor of hyperlipidemia and as an anti-obesity agent. In the present study, the pharmacological activity of BH extract (BHe) was observed in high-fat diet (HFD)-fed mice. Significant increases in fat pad weight, body weight, fat accumulation (body and abdominal fat density, and thickness of the periovarian and abdominal wall) and serum biochemical levels (aspartate transaminase, alanine amino-transferase, alkaline phosphatase, lactate dehydrogenase, γ-glutamyltransferase, total cholesterol, low-density lipoprotein and TG, with the exception of high-density lipoprotein) were observed in HFD-fed mice. In addition, increases in adipocyte hypertrophy, the area of steatohepatitis and hepatocyte hypertrophy were observed, whereas decreased zymogen content was identified upon histopathological observation. Increased deterioration of the endogenous antioxidant defense system (liver catalase, glutathione and superoxide dismutase) and hepatic lipid peroxidation was observed. In addition, there were decreases in hepatic glucokinase activity, AMPKα1 and AMPKα2 mRNA expression, adipose tissue uncoupling protein 2 expression, and adiponectin mRNA expression, increases in phosphoenolpyruvate carboxykinase and glucose-6-phosphatase activity, hepatic acetyl-CoA carboxylase 1 mRNA expression, and the expression of leptin, CCAAT/enhancer-binding protein (C/EBP) α, C/EBPβ and sterol-regulatory-element-binding protein 1c mRNA in the periovarian tissue. Furthermore, non-alcoholic fatty liver disease (NAFLD) and obesity were significantly inhibited by the continuous administration of BHe for 84 days. These results revealed that BHe may be a promising novel drug or functional food candidate for the treatment of obesity and NAFLD.

Proficiency of Broccoli (Brassice oleracea) Juice in Recovering of Testosterone Andriol-Induced Polycystic Ovary Syndrome Rats

The current study was designed to evaluate the efficiency of broccoli plant in therapy of PCOS that induced for the first time by testosterone andriol (T.A).
 Forty-eight immature female rats (21 days old) were divided into 6 groups (8 rats each) as follows: G1, animals were injected with sesame oil for 39 cascade days (control). G2, animals were injected with 1mg/100g b.w of T.A for 39 cascade days. G3, animals were injected with 1mg/100g b.w of T.A gathered with gavaged broccoli juice (b.j) for 39 cascade days. G4, animals were injected with sesame oil for cascade 39 days at the end of last injection were gavaged with d.w for 30 cascade days. G5, animals were injected with 1 mg/100g b.w of T.A for 39 cascade days and at the end of last injection were gavaged with d.w for 30 cascade days. G6, animals were injected with 1mg/100g b.w of T.A for 39 days and at the end of the last injection were gavaged with b.j for 30 cascade days. T.A-induced PCOS rats (G2 and G5) in comparison with controls (G1 and G4) exhibited that had a significant (P≤0.01) increase in the b.w, ovarian, uterine and fat pads weights as well as the fat cells diameter. Additionally, these groups had acyclicity, high numbers of ovarian cysts, atretic and preantral follicles in the ovaries, lowering the number and the diameter of C.L., and uterine changes. The levels of T, E and LH, an insulin, glucose, LDL, cholesterol in the serum were increased whereas the levels of FSH, LDH were decreased.
 Therefore, T.A PCOS model could be appropriated for studied all the features of syndrome i.e, ovarian, metabolic and endocrinologiccal disturbances. Whereas all these measurements of G3 and G6 were ameliorated and recovered into their normalcy. Our findings have shown the benefit of consuming broccoli in the protection (G3) and prevention (G6) of PCOS.

EVALUATION OF ANTI DIABETIC DRUG ALOGLIPTIN FOR THE TREATMENT OF OBESITY IN RATS

Obesity is a complex disease caused by the interaction of a myriad of genetic, dietary, lifestyle, and environmental factors, which favors a chronic positive energy balance, and leads to increased body fat mass. The incidence of obesity is rising at an alarming rate and is becoming a major public health concern with incalculable social costs. Indeed, obesity facilitates the development of metabolic disorders such as diabetes, hypertension, and cardiovascular diseases in addition to chronic diseases such as stroke, osteoarthritis, sleep apnea, some cancers, and inflammation based pathologies. Standard reference Sibutramine produced a significant anti obesity activity in HFD induced obesity in rats. Alogliptin with medium and high doses exhibited a significant anti obesity activity by reducing the body weight, food intake, organ and fat pads weight and serum GLU, CHO, TRG, LDL and VLDL cholesterol levels with an increased HDL levels in HFD induced obesity models in rats.
 Keywords: Alogliptin, Anti-obesity, Anti-diabetics, DPP-4

Duration of a "Brown-Like" Phenotype of White Adipose Tissue Induced by the β3 Agonist CL-316,243.

"Browning" i. e. the transformation of white adipose tissue into brown-like adipose tissue could induce efficient burning of excess fat reserves via induction of non-shivering thermogenesis. For example, activation of ß3 adrenergic receptors has been show to induce such changes, however, it is still not clear, how long after termination of such a treatment, beneficial effects might be maintained. To address this question, we treated rats s.c. for 2 weeks with the ß3 agonist CL-316,243 at 1 mg/kg and assessed interscapular brown fat and inguinal white fat pads weight, UCP-1 (a marker for the brown-like fat phenotype) using immunohistochemistry and H&E staining, at different intervals after treatment termination.One 1 day after the treatment cessation there was a decrease of inguinal white fat pad weight and increase of interscapular fat pad. This change vanished at 7 days for inguinal pad and at 14 days for interscapular pad. Histological analysis of interscapular pads showed increased UCP-1 staining and brown-like morphology in H&E staining slices at 1 day, but not other time points. In case of inguinal pad there were brown-like features in H&E slices at 1 day and less after 7 days, but absent at 14 days. UCP-1 staining was only detected 1 day after the treatment.In conclusion, the present results indicate that browning-like changes of white fat may be short lasting after treatment termination and could require maintenance treatment of inductor to achieve desired therapeutic effect. This might be a serious shortcoming of potential therapeutic use.

Abstract 003: Mrap2 Dissociate Mc4r-Mediated Sympathetic Control of Metabolism and Blood Pressure

The brain melanocortin-4 receptor (MC4R) plays an important in the control of food intake and energy expenditure by increasing thermogenic sympathetic nerve activity (SNA). In addition, brain MC4R-mediated activation of SNA subserving cardiovascular organs such as the kidneys increase blood pressure. The melanocortin receptor accessory protein 2 (MRAP2) regulates the activity of the MC4R and other G-protein coupled receptors, but its specific role in MC4R-containing neurons is not clear . We hypothesized that MRAP2 in MC4R neurons is essential for the regulation of SNA, energy homeostasis and blood pressure. We generated mice (MRAP2 MC4R ) that lack MRAP2 in MC4R neurons by crossing MRAP2 fl/fl mice with MC4R Cre mice and confirmed Cre recombinase activity in MC4R neurons using td-Tomato reporter mice. Interestingly, the MRAP2 MC4R mice displayed obesity as indicated by the increased (p<0.05) body weight (males: 40.1±2.2 vs 32.9±0.9g in littermate controls, females: 28.6±2.8 vs 24.2±1.3g in controls at 16 weeks of age) and fat mass, but not lean mass. Weights of fat pads and liver were also significantly elevated in the MRAP2 MC4R relative to littermate controls. Food intake was increased in the MRAP2 MC4R mice relative to littermate controls (males: 4.7±0.3 vs 3.9±0.3g and females: 3.5±0.2 vs 2.8±0.2g). Glucose and insulin tolerance tests revealed impaired glucose tolerance and insulin-induced glucose clearance in MRAP2 MC4R mice compared to littermate controls. Baseline brown adipose tissue (BAT) SNA tended to be lower in MRAP2 MC4R mice relative to controls. Moreover, intracerebroventricular (icv) injection of MTII (MC4R agonist, 1 μg) increased BAT SNA in control mice (107±31%) but not in MRAP2 MC4R mice (18±24%, p=0.02). On the other hand, icv the MTII (1 and 2 μg)-induced increase in renal SNA (p=0.2) and blood pressure (p=0.4) was not different in MRAP2 MC4R (100±32% and 15±8mmHg, respectively) relative to controls (74±24% and 12±6mmHg). These findings support a critical role for MRAP2 in uncoupling neuronal MC4R-mediated control of regional sympathetic traffic impacting energy metabolism versus blood pressure.

Maternal diet impacts in vitro culture requirements for optimal embryo development

To determine the effect of maternal high fat diet and exogenous lipid provision in vitro on mouse embryo development and subsequent embryo outgrowth in an extended culture system. Research study IVF zygotes from mice fed either a High Fat (HFD) or Normal Diet (ND) for 8 wk were allocated into medium with two albumin supplements; 2.5 mg/mL fatty acid free (FAF) or lipid rich (AlbuMAX (ALBMX)) BSA. In vivo produced blastocysts (VIVO) were also obtained from ND and HFD mice. Embryos were moved to fibronectin coated chambers (Ibidi) and cultured in IVC1 medium (Cell Guidance Systems) for 72 h, then media was replaced with IVC2 and embryos cultured for an additional 48 h (D8.5). Embryos (ND ALBMX, 8; ND FAF, 10; ND VIVO, 6; HFD ALBMX, 8; HFD FAF, 8; HFD VIVO, 6) were fixed and assessed for outgrowth cell number (DAPI) and lipid volume (Nile Red). Lipid volume was normalized to total actin staining. Data are reported as mean ± SEM; significance p<0.05. Body weight was not different (ND, 25.6 ± 0.4g; HFD, 27.2 ± 0.9g). Abdominal fat pad weight was greater in high fat fed females (ND, 0.75 ± 0.10g; HFD, 1.27 ± 0.20g). There was no difference in embryo production between treatments, but there tended to be a higher percentage (P=0.10) of morulae produced in HFD FAF (77% ± 5.8) than ND FAF (58% ± 4.9). There was a higher percentage of hatched blastocysts in ND FAF (19% ± 4.6) than in HFD ALBMX (4% ± 2.2) and HFD FAF (5% ± 2.5%). Embryos from HFD females cultured in a low lipid environment were more successful in forming embryo outgrowths in extended culture (100%) than HFD embryos cultured with high lipid (62%). The total cell number of embryo outgrowths was significantly higher in ND in vivo produced embryos; there were no other differences between treatments (ND VIVO, 453 ± 56; ND FAF, 219 ± 46; ND ALBMX, 202 ± 56; HFD VIVO, 177 ± 61; HFD FAF 88 ± 56; HFD ALBMX,147 ± 52). There were no differences in the total amount of endogenous lipid (in relative fluorescence units) per embryo outgrowth (ND VIVO, 2.2 ± 0.9; ND FAF, 2.0 ± 0.8; ND ALBMX, 0.65 ± 1.1; HFD VIVO, 2.4 ± 1.1; HFD FAF 1.6 ± 1.2; HFD ALBMX, 1.1 ± 1.0). Embryos from mice fed a high fat diet, regardless of lipid provision in culture media, developed slower than embryos from mice fed a normal diet in lipid free conditions, suggesting reduced embryo quality. Interestingly, in vivo produced embryos and ND embryos cultured in lipid free conditions had the highest levels of endogenous lipid in outgrowth culture, suggesting embryos from obese females and those cultured under suboptimal lipid conditions may excessively metabolize endogenous lipids leading to reduced embryo quality. Additional experimentation will investigate this hypothesis. Manipulation of lipids in culture may optimize embryo quality, particularly from obese females.

The effect of rearing photoperiod on broiler breeder reproductive performance depended on body weight

ABSTRACTBody weight (BW) and rearing photoperiod are important factors affecting sexual maturation rate and reproductive performance in broiler breeders. The current experiment used a 2 × 3 factorial arrangement of treatments to study the interaction between BW and rearing photoperiod on reproductive performance in group housed broiler breeder hens, while minimizing variation in BW. Hens (n = 180) were fed with a precision feeding system to allocate feed individually to achieve the breeder-recommended target curve (Standard) or to a target curve that reached the 21 wk BW at 18 wk (High). Hens were on 8L:16D, 10L:14D, or 12L:12D photoschedules during rearing and were photostimulated at 21 wk with a 16L:8D photoschedule. Sexual maturity (defined as age at first egg) and individual egg production to 55 wk were recorded. At 55 wk, proportional weights of individual body components were determined by dissection. Differences were reported as significant at P ≤ 0.05. A significant interaction between BW and rearing photoschedule affected age at sexual maturity and egg production. In the High BW treatment, age at sexual maturity did not differ between hens under the 8L:16D and 10L:14D photoschedules (173 vs. 172 d, respectively). In the Standard BW treatment, the 12L:12D rearing photoperiod delayed sexual maturity compared with the 8L:16D rearing photoperiod (266 vs. 180 d, respectively). All hens on the High BW treatment laid at least 1 egg before the end of the experiment. Conversely, 3.3, 18.1, and 37.6% of Standard BW hens on the 8L:16D, 10L:14D, and 12L:12D photoschedules, respectively, never commenced egg production. At the end of the experiment, proportional breast weight was higher and proportional fatpad weight was lower in Standard compared to High BW hens (25.8 vs. 27.5% and 2.4 vs. 1.5% of BW, respectively). We conclude that increased BW partially counters the effect of longer photoschedules on sexual maturity in broiler breeders and that dissipation of the photorefractory state depends on BW.

High-fat diet leads to adiposity and adipose tissue inflammation: the effect of whey protein supplementation and aerobic exercise training.

There is little understanding about dietary proteins and their potential contribution to obesity-induced inflammation. This study investigates the effect of 10 weeks of aerobic training and whey protein (WP) supplementation on visceral adipose tissue inflammation in rats fed a high-fat diet (HFD). In the first phase, which lasted 9 weeks, 40 male Wistar rats were randomly divided into 2 groups: (1) normal diet (n = 8), and (2) HFD (n = 32). In the second phase, rats fed an HFD were randomly assigned into 4 groups (n = 8/group): (1) sedentary, (2) WP, (3) aerobic training, and (4) WP + aerobic training. The aerobic training was performed for 10 weeks, 5 days/week at 21 m/min, 15% incline, for 60 min/day. HFD significantly increased body weight, adiposity index, fat pads weight, glucose levels, and insulin resistance index compared with the normal diet. Also, levels of tumor necrosis factor alpha (TNF-α), monocyte chemoattractant protein-1 (MCP-1), hypoxia inducible factor 1 alpha (HIF-1α), and vascular endothelial growth factor A (VEGF-A) in adipose tissue and serum levels of TNF-α were increased in the HFD group. Glucose levels, insulin resistance index, and triglycerides were reduced only by WP, independently of aerobic training. Both the aerobic training and WP reduced the fat pads weight and levels of TNF-α, HIF-1α, and VEGF-A in adipose tissue. Nevertheless, the levels of MCP-1 in adipose tissue and serum levels of TNF-α and MCP-1 were not reduced significantly by WP or aerobic training. These findings suggest that both aerobic training and WP supplementation lead to a reduction in adiposity and ameliorate obesity-induced inflammation in visceral adipose tissue.

Anti-obesity potential of Glycyrrhiza uralensis and licochalcone A through induction of adipocyte browning

The main function of brown adipose tissue is to dissipate surplus caloric intake into heat energy by thermogenesis, increasing energy expenditure. Inducible brown adipocytes can develop within white adipose tissue (WAT) through a process referred to as browning. Browning of white fat represents a promising strategy for treatment of obesity and the related complications. We investigated whether Glycyrrhiza uralensis and its ingredients modulated adipogenesis through adipocyte browning using 3T3-L1 adipocytes and a high-fat diet (HFD)-induced obesity mice model. Amongst extracts and fractions of G. uralensis, methyl dichloride (MeCl2) fraction was the most effective to induce expression of uncoupling protein 1 (UCP1), a fat browning marker, in 3T3-L1 adipocytes. Ingredients of G. uralensis such as licochalcone A (LicoA), isoliquiritigenin, and liquiritigenin induced UCP1 expression in 3T3-L1 adipocytes. After inducing obesity in mice by 6-week HFD, MeCl2 fraction of G. uralensis or LicoA was intraperitoneally administered for additional 19 days. MeCl2 fraction or LicoA significantly reduced body weight gain and inguinal fat pad weights. Furthermore, MeCl2 fraction or LicoA improved metabolic disorders induced by HFD as the treatments decreased serum levels of glucose and cholesterol, and blocked insulin resistance. MeCl2 fraction or LicoA enhanced expression of brown fat markers such as UCP1, PRDM16, and PGC-1α and increased brown fat phenotype population in inguinal WAT of HFD-fed mice. Our results demonstrate that G. uralensis and LicoA are effective to reduce obesity and to recover metabolic homeostasis by inducing the brown fat phenotype.

Lifetime productivity of conventionally and precision-fed broiler breeders.

ABSTRACTA precision feeding (PF) system was developed to increase broiler breeder lifetime reproductive performance through improved flock uniformity. The current study consisted of 2 rearing and 3 laying treatments. From 0 to 22 wk of age, 480 Cobb male grandparent line pullets and 80 Cobb MX males were fed once daily as a group (CON), or individually with a PF system. Pullets were housed in 6 replicate pens of 40 birds, and cockerels in one pen per treatment. During lay, CON and PF treatments continued, and a third treatment was added, where PF-reared birds were transitioned to conventional feeding (PFCON; n = 3 pens). At photostimulation (22 wk of age), all pens had 24 hens and 2 roosters. Birds were allowed to mate naturally to 52 wk. Analysis of variance was conducted, and Tukey-adjusted means were reported as different where P ≤ 0.05. Mean BW was near the target BW in all treatments. At photostimulation, PF pullet BW CV was 2% vs 14% in CON pullets. Cumulative feed conversion ratio during rearing was lower in PF treatment pullets, which ate 3% less than CON pullets. Pullets in the PF treatment received 10 meals spread throughout each day, compared with one meal per day in the CON treatment. Increased feeding frequency would reduce diurnal fluctuations in nutrient supply, which may explain why PF pullets had 1.2 times the breast muscle weight of CON pullets at 22 wk. There was no treatment difference in abdominal fatpad weight at 22 wk. The PF treatment had 3.8% higher fertility and 1.3% lower egg weight CV compared with the CON treatment. Egg production in PF and PFCON treatments was 0.73 and 0.89 times that of the CON treatment, respectively. It is hypothesized that metabolic changes in PF pullets provided an insufficient metabolic trigger for sexual maturation. It follows that relaxing feed restriction may increase fat deposition and egg production in PF broiler breeders.

Sexual-Dimorphism in Exercise-Induced Beiging and Altered Mitochondrial Function in Inguinal White Adipose Tissue (iWAT) from the Mouse

Regular physical exercise has numerous benefits on metabolic health, likely involving adaptations to many tissues, including adipose tissue. There are conflicting reports on the effects of exercise training on adaptations to iWAT and we hypothesized that these discrepancies may stem in part from sex-specific differences. Male and female 10 week old C57BL6/J mice were housed in cages with (trained) or without (sedentary) running wheels for 11 days (n=6-9/sex/experiment). Males performed less voluntary exercise vs. females (56±7 vs. 78±5 km; p&amp;lt;0.05). In males, training decreased iWAT fat pad weight (19.6%) and adipocyte size (19%) (both p&amp;lt;0.05), whereas training did not have these effects on iWAT in females, most likely due to increased food intake. Training did not alter perigonadal WAT weight or adipocyte size in either sex. In iWAT, training in males increased mRNA of the beiging genes Ucp1 (304%; p&amp;lt;0.01); Pgc1α (228%; p&amp;lt;0.05); Cidea (206%; p&amp;lt;0.05); and Dio2 (197%; p&amp;lt;0.01), as well as Ucp1 protein (124%; p&amp;lt;0.01), but none of these markers were increased in females. Exercise training also increased mitochondrial parameters in iWAT only from males, including basal respiration (170%; p&amp;lt;0.01), glycolytic capacity (227%; p&amp;lt;0.001) and the mitochondrial fission genes Opa1 (235%; p&amp;lt;0.05), Mfn1 (231%; p&amp;lt;0.001), and Mfn2 (229%; p&amp;lt;0.01). Since exercise may increase testosterone in male mice, we tested the effects of testosterone on iWAT beiging and mitochondria. iWAT of male and female mice were treated with testosterone (10μM) for 24 hours. Interestingly, testosterone increased Ucp1 protein (175%; p&amp;lt;0.05) and mRNA (386%; p&amp;lt;0.05) in iWAT from male, but not in females. We conclude that voluntary wheel running in mice results in beiging and mitochondrial adaptations to iWAT exclusively in males. Sex-specific differences in WAT function will be important to consider in all research investigating adipose tissue beiging and mitochondrial function. Disclosure P. Nigro: None. R. Middelbeek: None. C.R. Alves: None. B.G. Albertson: None. L.A. Rowland: None. A.B. Wagner: None. N.B. Prince: None. M.F. Hirshman: None. L.J. Goodyear: None.

Multigenerational effects of a reduced balanced protein diet during the rearing and laying period of broiler breeders. 1. Performance of the F1 breeder generation

Studies on mammals and poultry showed that maternal dietary treatments can alter the offspring performance. However, in contrast to rodent studies, little is known about multigenerational dietary manipulations in broiler breeders. The presented research aimed to investigate the effects of a reduction of 25% in the dietary crude protein (CP) level in the F0 generation on the body composition and reproductive performance of F1 broiler breeders. In the F0 generation, breeders were fed either a control (C) or reduced balanced protein (RP) diet, 25% reduction in crude protein and amino acids. Female F0-progeny of each treatment were fed a C or RP diet, resulting in 4 treatments in the F1 breeder generation: C/C, C/RP, RP/C, and RP/RP. The reproductive performance of breeders fed RP diets was negatively influenced by the dietary CP reduction in the F1 generation (P < 0.001). Moreover, breeders descending from hens that received RP diets in the F0 generation showed a significantly reduced reproductive capacity compared to their control fed counterparts (P < 0.001). Breeders fed RP diets in the F1 generation were characterized by higher plasma T3 concentrations (P < 0.001), an increased proportional abdominal fat pad (P < 0.001) and proportional liver weight (P < 0.001). During the rearing phase, the RP fed breeders needed a higher feed allowance, whereas no differences could be observed between the C/C and RP/C or the C/RP and RP/RP breeders. However, breeders originating from birds fed RP diets in the F0 generation needed lower feed allocations in the laying phase to maintain a similar body weight. Egg weight was reduced for the C/RP and RP/RP breeders. At 34 wk of age, eggs from C/RP and RP/RP breeders showed a reduced proportional albumen weight, whereas no effects on egg composition were found at 42 wk of age. It was concluded that prenatal protein undernutrition triggered hens to relocate more energy towards growth and maintenance and less towards reproductive capacity.

Anti-Obesity Effect of Arq Zeera and Its Main Components Thymol and Cuminaldehyde in High Fat Diet Induced Obese Rats.

Arq zeera is a distillate product that prepared from four different herbs namely Trachyspermum ammi L., apiaceae, Zingiber officinale Roxb., zingiberaceae, Carum carvi L.,apiaceae and Cuminum cyminum L., apiaceae. The present study aims to determine the antiobesity effect of arq zeera and its main components thymol and cuminaldehyde in high fat diet induced obese rats and to explore its mechanism of action. In current study, orlistat was used as positive controls. Male Wistar rats were fed with HFD for 42 days to induce obesity. HFD-fed rats were administered with arq zeera, thymol, cumic aldehyde, thymol + cuminaldehyde and orlistat for 28 days. During the course of treatment, body weight and food intake frequently observed and after end of treatments, liver weight, visceral fat pad weight, plasma lipid proflie, alanine aminotransferase, aspartate aminotransferase, glucose, insulin, leptin levels and pancreatic lipase activity were studied on all treated obese rats. The histopathology of liver was also studied. After the treatments of arq zeera and its main components, body weight, food intake, liver weight, visceral fat pad weight and the level of lipid profile, alanine aminotransferase, aspartate aminotranferase, glucose, insulin, and leptin were found to be decreased and pancreatic lipase inhibition were increased. Arq zeera showed more potential antiobesity effect than orlistat. According to our present findings, arq zeera and its main components possessed potent antiobesity effect on high fat diet -induced obese rats and excreted anti-obesity effect partly via hypolipidemic, hypoglycemic, hypoinsulinemic, hypoleptinemic and pancreatic lipase inhibition action.

Effects of exercise training on adipose tissue apelin expression in streptozotocin-nicotinamide induced diabetic rats

Apelin is an adipocyte-derived peptide that plays an important role in regulation of energy homoeostasis and decrease of insulin resistance. We investigated the effects of exercise training on adipose tissue apelin expression in streptozotocin-nicotinamide induced diabetic rats. In this experimental study, 38 male Wistar rats were assigned to 4 groups: sedentary non-diabetic, trained non-diabetic, sedentary diabetic and trained diabetic. Type 2 diabetes mellitus (T2DM) was induced by intraperitoneal injection of streptozotocin and nicotinamide in adult rats. The trained groups ran 8-week on treadmill progressively for 45 min at a speed of 24 m/min and a 5% grade. After the training period, an intraperitoneal glucose tolerance test was performed in addition to the measurement of blood lipids and plasma apelin levels. Apelin mRNA levels in visceral adipose tissue were also analyzed. Two-way repeated measures analysis of variance (ANOVA) and Pearson correlation coefficient was used for analyzing data. P < 0.05 was considered to be statistically significant. Results indicated a significant decrease of insulin resistance followed by a significant increase of plasma levels and mRNA expression of apelin in trained diabetic compared with sedentary diabetic rats. Furthermore, apelin levels did not correlate significantly with body weight and epididymal fat weight in trained diabetic rats. In conclusion, the findings revealed that chronic exercise training, independently of body weight and fat pad weight by decrease of insulin resistance can increase apelin levels in visceral adipose tissue, thereby attenuating the progression of diabetes and decreasing insulin resistance in T2DM rats.

Protein-restriction diet during the suckling phase programs rat metabolism against obesity and insulin resistance exacerbation induced by a high-fat diet in adulthood

Protein restriction during the suckling phase can malprogram rat offspring to a lean phenotype associated with metabolic dysfunctions later in life. We tested whether protein-caloric restriction during lactation can exacerbate the effect of a high-fat (HF) diet at adulthood. To test this hypothesis, we fed lactating Wistar dams with a low-protein (LP; 4% protein) diet during the first 2 weeks of lactation or a normal-protein (NP; 23% protein) diet throughout lactation. Rat offspring from NP and LP mothers received a normal-protein diet until 60 days old. At this time, a batch of animals from both groups was fed an HF (35% fat) diet, while another received an NF (7% fat) diet. Maternal protein-caloric restriction provoked lower body weight and fat pad stores, hypoinsulinemia, glucose intolerance, higher insulin sensitivity, reduced insulin secretion and altered autonomic nervous system (ANS) function in adult rat offspring. At 90 days old, NP rats fed an HF diet in adulthood displayed obesity, impaired glucose homeostasis and altered insulin secretion and ANS activity. Interestingly, the LP/HF group also presented fat pad and body weight gain, altered glucose homeostasis, hyperleptinemia and impaired insulin secretion but at a smaller magnitude than the NP-HF group. In addition, LP/HF rats displayed elevated insulin sensitivity. We concluded that protein-caloric restriction during the first 14 days of life programs the rat metabolism against obesity and insulin resistance exacerbation induced by an obesogenic HF diet.

The role of ACE2/Ang 1–7/Mas axis in the white adipose tissue for the prevention of obesity and insulin resistance through aerobic exercise training

The activation of angiotensin converting enzyme 2 (ACE2)/angiotensin 1–7 (Ang 1–7)/receptor Mas axis has been associated with cardiovascular and metabolic improvement, and may represent a new therapeutic target for cardiometabolic diseases. Aerobic exercise training (AET) has been widely used for the prevention and treatment of obesity and insulin resistance (IR). In the present study we evaluated if the prevention of obesity and IR through AET is associated with changes in the ACE2/Ang (1–7)/Mas axis in the white adipose tissue (WAT). Adult male C57BL6/J mice were assigned into chow‐fed controls (C, n=5), chow‐fed trained (T, n=5), cafeteria diet (CAF, n=5), and cafeteria diet plus trained (CAFT, n=5). AET was performed simultaneously with diet and consisted of 8‐wk running session of 60 min at 60% of maximal speed, 5 days/wk. Experimental procedures were approved by Ethics Committee from Faculty of Medicine of University of São Paulo (#002/15). The body weight of the T and CAFT groups were lower from the third week of experimental protocol compared to C. The CAF group had higher retroperitoneal and subcutaneous (SC) fat pads weights compared to C, but the AET was able to prevent these increases in the CAFT group. Periepididimal (PE) fat pad weight was lower in T group compared to other groups. Cafeteria diet induced glucose intolerance and IR in CAF group (AUC: 35200± 1076 mg/dL/120 min; kITT: 2.5 ± 0.17 %/min) compared to the C group (AUC: 28333±1305 mg/dL/120 min; kITT: 3.7 ± 0.21 %/min), which were counteracted by AET in CAFT group (AUC: 28896 ± 1133 mg/dL/120 min; kITT: 3.9 ± 0.33 %/min). In the PE‐WAT, the activity of ACE2 was higher in CAF and CAFT groups compared to C and T groups, but Ang 1–7 concentration and Mas protein expression were not different among groups. In the SC‐WAT, no differences were found in ACE2 activity and Mas protein expression, but the Ang 1–7 concentration was lower in CAF and CAFT compared to C and T groups. In conclusion, the prevention of obesity and IR by AET was independent of the ACE2/Ang 1–7/Mas axis activation in the visceral and subcutaneous WAT.Support or Funding InformationSupport: FAPESP #2015/04948‐4; #2016/23783‐9.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Effect of long‐term administration of heat‐processed onion (Allium cepa L.) extract on body weight, visceral fat accumulation, and plasma lipid profile in C57BL/6 mice fed high‐fat diets

In the previous study, it was found that Amadori rearrangement compounds‐rich heat‐processed onion reduced postprandial blood glucose increase by reducing absorption of glucose through inhibition of sucrase and α‐glucosidase in the small intestinal tract. This reduced absorption of carbohydrate might control body weight gain due to excessive carbohydrates consumption and induce calorie restriction. To investigate and prove the mechanism for the effects of heat‐processed onion extract (ONI_V) on body weight gain, body weight, plasma lipids, body fat mass, and lipid deposition were evaluated and compared to Garcinia cambogia (GC), a known competitive inhibitor of adenosine 5′‐triphosphate (ATP) citrate lyase in C57BL/6 mice model. Male C57BL/6 mice were fed high‐fat diet (60% kcal fat) with 2% ONI_V or GC used as a positive control. Supplementation of ONI_V effectively lowered the body weight gain, visceral fat accumulation, and plasma lipid concentrations. Compared to control, ONI_V increased the number of adipocytes with a smaller diameter. Interestingly, GC treatment did not change either adipocyte numbers or sizes although total weight of visceral fat pads was significantly reduced compared to control. These results indicate that ONI_V and GC may use different mechanisms in inhibiting weight gain under the current experimental conditions used in this study. Furthermore, ONI_V may reduce weight gain using a similar mechanism of anti‐diabetic drugs, thiazolidinediones (TZDs). TZDs in humans and animals have been shown to be a strong ligand for PPARγ, a nuclear transcription factor that enhances adipocyte differentiation, thereby increasing the number of adipocytes with smaller diameters, which is consistent with the effects of ONI_V observed in this study. According to the obtained results, ONI‐V may be effective not only in reducing weight gains, but also in ameliorating some of the metabolic abnormalities including hyperglycemia, oxidative stress, and inflammation associated with weight gain and obesity.Support or Funding InformationThis research was financially supported by the Ministry of Trade, Industry, and Energy (MOTIE), Korea, under the “Regional Specialized Industry Development Program” supervised by the Korea Institute for Advancement of Technology (KIAT).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Long-Chain Omega-3 Polyunsaturated Fatty Acids Modulate Mammary Gland Composition and Inflammation

Studies in rodents have shown that dietary modifications as mammary glands (MG) develop, regulates susceptibility to mammary tumor initiation. However, the effects of dietary PUFA composition on MGs in adult life, remains poorly understood. This study investigated morphological alterations and inflammatory microenvironments in the MGs of adult mice fed isocaloric and isolipidic liquid diets with varying compositions of omega (ω)-6 and long-chain (Lc)-ω3FA that were pair-fed. Despite similar consumption levels of the diets, mice fed the ω-3 diet had significantly lower body-weight gains, and abdominal-fat and mammary fat pad (MFP) weights. Fatty acid analysis showed significantly higher levels of Lc-ω-3FAs in the MFPs of mice on the ω-3 diet, while in the MFPs from the ω-6 group, Lc-ω-3FAs were undetectable. Our study revealed that MGs from ω-3 group had a significantly lower ductal end-point density, branching density, an absence of ductal sprouts, a thinner ductal stroma, fewer proliferating epithelial cells and a lower transcription levels of estrogen receptor 1 and amphiregulin. An analysis of the MFP and abdominal-fat showed significantly smaller adipocytes in the ω-3 group, which was accompanied by lower transcription levels of leptin, IGF1, and IGF1R. Further, MFPs from the ω-3 group had significantly decreased numbers and sizes of crown-like-structures (CLS), F4/80+ macrophages and decreased expression of proinflammatory mediators including Ptgs2, IL6, CCL2, TNFα, NFκB, and IFNγ. Together, these results support dietary Lc-ω-3FA regulation of MG structure and density and adipose tissue inflammation with the potential for dietary Lc-ω-3FA to decrease the risk of mammary gland tumor formation.

Osteopontin-deficient progenitor cells display enhanced differentiation to adipocytes

ObjectiveOsteopontin (OPN, Spp1) is a protein upregulated in white adipose tissue (WAT) of obese subjects. Deletion of OPN protects mice from high-fat diet-induced WAT inflammation and insulin resistance. However, the alterations mediated by loss of OPN in WAT before the obesogenic challenge have not yet been investigated. Therefore, we hypothesised that the lack of OPN might enhance the pro-adipogenic micro environment before obesity driven inflammation. MethodsOPN deficiency was tested in visceral (V) and subcutaneous (SC) WAT from WT and Spp1−/− female mice. Gene expression for hypoxia, inflammation and adipogenesis was checked in WT vs. Spp1−/− mice (n=15). Adipocytes progenitor cells (APC) were isolated by fluorescence cell sorting and role of OPN deficiency in adipogenesis was investigated by cell images and RT-PCR. ResultsWe show that Spp1−/− maintained normal body and fat-pad weights, although hypoxia and inflammation markers were significantly reduced. In contrast, expression of genes involved in adipogenesis was increased in WAT from Spp1−/− mice. Strikingly, APC from Spp1−/− were diminished but differentiated more efficiently to adipocytes than those from control mice. ConclusionsAPC from SC-WAT of lean OPN-deficient mice display an enhanced capacity for differentiating to adipocytes. These alterations may explain the healthy expansion of WAT in the OPN-deficient model which is associated with reduced inflammation and insulin resistance.

Nordihydroguaiaretic Acid, a Lignan from Larrea tridentata (Creosote Bush), Protects Against American Lifestyle-Induced Obesity Syndrome Diet-Induced Metabolic Dysfunction in Mice.

To determine the effects of nordihydroguaiaretic acid (NDGA) on metabolic and molecular changes in response to feeding a typical American fast food or Western diet, mice were fed an American lifestyle-induced obesity syndrome (ALIOS) diet and subjected to metabolic analysis. Male C57BL/6J mice were randomly assigned to the ALIOS diet, the ALIOS diet supplemented with NDGA (NDGA+ALIOS), or a control diet and were maintained on the specific diet for 8 weeks. Mice fed the ALIOS diet showed increased body, liver, and epididymal fat pad weight as well as increased plasma alanine transaminase (ALT) and aspartate aminotransferase (AST) levels (a measure of liver injury) and liver triglyceride content. Coadministration of NDGA normalized body and epididymal fat pad weight, ALT and AST levels, and liver triglycerides. NDGA treatment also improved insulin sensitivity but not glucose intolerance in mice fed the ALIOS diet. In mice fed the NDGA+ALIOS diet, NDGA supplementation induced peroxisome proliferator-activated receptor α (PPARα; the master regulator of fatty acid oxidation) and mRNA levels of carnitine palmitoyltransferases Cpt1c and Cpt2, key genes involved in fatty acid oxidation, compared with the ALIOS diet. NDGA significantly reduced liver endoplasmic reticulum (ER) stress response C/EBP homologous protein, compared with chow or the ALIOS diet, and also ameliorated ALIOS diet-induced elevation of apoptosis signaling protein, caspase 3. Likewise, NDGA downregulated the ALIOS diet-induced mRNA levels of Pparg, fatty acid synthase Fasn, and diacylglycerol acyltransferase Dgat2 NDGA treatment of ALIOS-fed mice upregulated the hepatic expression of antioxidant enzymes, glutathione peroxidase 4, and peroxiredoxin 3 proteins. In conclusion, we provide evidence that NDGA improves metabolic dysregulation by simultaneously modulating the PPARα transcription factor and key genes involved in fatty acid oxidation, key antioxidant and lipogenic enzymes, and apoptosis and ER stress signaling pathways.