Plasma leptin and insulin in C57BI/6J mice on a high-fat diet: relation to subsequent changes in body weight

It has been proposed that leptin and insulin through central effects are involved in the regulation of energy balance and body weight. Whether circulating leptin or insulin levels predict subsequent changes in body weight is, however, not known. We examined plasma leptin and insulin at 2, 3, 6, 9 and 12 months of age in C57BI/6J mice given a normal diet (n = 12) or a high-fat diet (58% fat on a caloric base; n = 15). Plasma leptin levels increased by age and correlated with body weight in the entire material (r = 0.81, P < 0.001). Also plasma insulin increased by high-fat diet and correlated across all age periods with body weight (r = 0.56, P < 0.001). In mice, given normal diet, plasma leptin or insulin did not correlate to subsequent changes in body weight at any of the time points studied. However, in mice given the high-fat diet, plasma leptin at 6 (r = -0.57, P = 0.027) and 9 months of age (r = -0.56, P = 0.042) as well as plasma insulin at 6 (r = - 0.51, P = 0.049) and 9 months (r = -0.58, P = 0.037) correlated inversely to the change in body weight during the subsequent 3-month period. Hence, both leptin and insulin are negative predictors for future weight gain in high-fat fed mice. This suggests that when the regulation of body weight is challenged by a high-fat diet, leptin and insulin act to restrain or prevent future weight gain. This in turn may suggest that impairment of these (probably central) actions of leptin and insulin might underlie excessive increase in body weight under such conditions.     

Effects of replacing wheat flour with detoxified ginkgo nut powder on lipid metabolism of obese C57BL/6J male mice

Effects of detoxified ginkgo nut powder (DGP) on lipid metabolism of obese mice were evaluated. Mice were divided into four groups: normal group (NC), hyperlipidaemic group (HC, high-fat feed), HC/DGP group (high-fat diet?+?DGP), and HC/flour group (HC/WF, high-fat diet?+?flour). After 18 weeks, liver and body fat weights of HC/DGP were significantly lower than those of HC and HC/WF, but similar to those of NC. The serum and hepatic levels of serum triglyceride, total cholesterol, low-density lipoprotein cholesterol, leptin and resistin in HC/DGP were similar to those in NC but significantly lower than those in HC and HC/WF. In addition, the expression levels of PPARα (peroxisome proliferator-activated receptor alpha) in liver and of hormone-sensitive lipase, adipose triglyceride lipase, and monoacylglycerol lipase in epididymal fat were higher in HC/DGP than in other groups. The results revealed that DGP may reduce inflammation and promote normal lipid metabolism.     

Intraventricular insulin and leptin reduce food intake and body weight in C57BL/6J mice

As the incidence of obesity continues to increase, adequate animal models acquire increased importance for the investigation of energy homeostatic mechanisms. Understanding the central mechanism of action of the adiposity hormones, insulin and leptin, has become particularly important as researchers examine ways to treat or prevent obesity. Although the intra-3rd-ventricular (i3vt) administration of insulin reduces food intake in several species, its effects on food intake and body weight have not been previously been assessed in mice. Male C57BL/6J mice were administered insulin i3vt (0.05, 0.1 or 0.4 microU) or leptin i3vt (5 microg/1 microl) as a positive control. As it occurs in other species, i3vt insulin dose-dependently reduced 24-h food intake and body weight, and increased hypothalamic proopiomelanocortin (POMC) mRNA. Hence, genetic manipulations that influence brain insulin sensitivity in mice can now more easily be integrated with the broader literature on energy homeostasis.     

谷氨酰胺对高脂饮食诱导C57BL/6J小鼠肥胖和胰岛素抵抗的影响

目的:探讨谷氨酰胺(L-glutamine,Gln)对高脂饮食(high-fat diet,HFD)诱导小鼠肥胖和胰岛素抵抗的影响。方法:60只雄性C57BL/6J小鼠随机分为正常对照(normal control,NC)组、HFD组、HFD+丙氨酸(Lalanine,Ala)组和HFD+Gln组,每组15只。每周记录小鼠体重,给药16周后禁食不禁水12 h测定空腹血糖(fasting blood glucose,FBG),处死后剖腹取附睾脂肪垫并称重。采用酶联免疫法检测小鼠胰岛素(insulin,INS)、瘦素(leptin,LEP)、脂联素(adiponectin,APN)和胰高血糖素样肽1(glucagon-like peptide-1,GLP-1)的水平,并计算胰岛素抵抗指数(insulin resistance index,IRI)和胰岛素敏感指数(insulin sensitivity index,ISI)。结果:与NC组比较,HFD组小鼠体重和附睾脂肪垫重量明显升高,FBG、INS、IRI和LEP水平均明显升高,ISI和APN水平明显降低(P0.05);与HFD组比较,HFD+Gln组小鼠体重明显下降,FBG和LEP水平明显降低,IRI明显减小(P0.05)。4组小鼠血清的GLP-1水平差异无统计学显著性。结论:谷氨酰胺减轻高脂饮食诱导的肥胖小鼠体重和胰岛素抵抗。     

Behavior and body weight changes under intermittent exposure to cold in C57BL/6J mice

This experiment examined effects of the intermittent exposure to cold. C57BL/6J mice were exposed to cold (4-5 degrees C) for six hours in light (L-cold group) or dark (D-cold group) period and their wheel-running and drinking activities, daily amounts of food and water intake, and body weight were analyzed. Wheel running and drinking decreased during cold exposure, while they increased in postcold period. These behavioral changes were more clearly found in the D-cold group. Body weight of the D-cold group was kept constant for all days of cold exposure, while that of the L-cold group tended to increase. These results are discussed from the view points of adaptive significance of postcold behaviors and the relationship between behavioral and physiological adaptations.     

Decreased irisin secretion contributes to muscle insulin resistance in high-fat diet mice

Aims: Recent studies have revealed the relationship between irisin and insulin signaling, while positive associations of muscle FNDC5 with insulin resistance is observed. However, the functional mechanism of irisin on muscle insulin resistance is still obscure. This study aims to investigate the effect of irisin on muscle insulin action. Methods: Diabetic mouse model was established by high fat diet (HFD) induced obesity in C57BL/6 mice. Body indexes and serum levels of triglyceride (TG), blood glucose and insulin were record. Oral glucose tolerance test (OGTT) was performed before being killed. Circulating irisin level was also detected, while FNDC5/irisin expression was determined by RT-PCR and western blot analysis in both muscle and adipose tissues. Insulin action was further evaluated by the phosphorylation of AKT and Erk, and palmitic acid treated muscle cells were introduced for mimicking diabetic status in vitro. Results: Obvious obese feathers associated with type 2 diabetes were observed in HFD feeding mice, with decreased circulating irisin level and FNDC5/irisin secretion in adipose tissues. Although FNDC5/irisin expression showed little change in skeletal muscle, the insulin action was inhibited significantly. Moreover, palmitic acid treated muscle cells showed similar inhibition of insulin action, and FNDC5/irisin expression change. Besides, insulin action could be reversed by irisin addition in muscle cells. Conclusion: HFD induced obese mice showed decreased irisin secretion from adipose tissues, which might contribute to muscle insulin resistance. Furthermore, irisin addition could recover insulin action in palmitic acid treated muscle cells, indicating the importance of irisin for preserving insulin signaling.     

Determination of oxidation phenotype in inbred C57Bl/6 and BALB/C mice

Research Laboratory of Pharmacogenetics, aand Research Laboratory of Pharmacokinetics, Institute of Pharmacology, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR A. V. Val'dman.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 110, No. 11, pp. 491–493, November, 1990.     

Gene expression in livers of BALB/C and C57BL/6J mice fed a high-fat diet

We previously demonstrated that high-fat diet (HFD)-induced hepatic lipid accumulation is more severe in BALB/c mice than in C57BL/6J (B6) mice. To understand the changes in liver metabolism, we studied blood chemistry, gene expression, and histopathological changes of the liver in nine-week HFD-fed BALB/c and B6 mice and one- or four-week HFD-fed BALB/c mice. Serum total cholesterol and triglyceride levels were significantly increased in all HFD-fed groups, and one- and four-week HFD-fed BALB/c groups, respectively. Histopathology revealed that vacuolation of hepatocytes was severe in nine-week HFD-fed BALB/c mice, although it was less severe in the other groups. Microarray analysis of mRNA expression of nine-week HFD-fed BALB/c mice showed up-regulation of genes involved in fatty acid uptake and biosynthesis, such as Cd36, Acaca, Acly, and Fasn. Some changes were observed in the one- and four-week HFD-fed BALB/c groups and the nine-week HFD-fed B6 group, however these changes in mRNA expression were not so marked. In conclusion, the fatty accumulation observed in BALB/c mice may be caused, at least in part, by up-regulation of fatty acid uptake and biosynthesis. Cd36, Acaca, Acly and Fasn may be involved in these metabolic processes.     

Morphoquantitative analysis of the Ileum of C57BL/6 mice (Mus musculus) fed with a high-fat diet

Due to the increase in overweight and obesity in humans, various studies have been conducted in recent years that demonstrate the detrimental effects on tissues and organs. The aim of this study was to assess the morphoquantitative changes produced in the ileum of mice, associated with high-fat diets. Fourteen male C57BL/6 mice, 5 months old, were fed two types of diets for 14 weeks. The control group (C) was fed a standard diet (10% fat, AIN-93M) and the experimental group (E) was fed a high-fat diet (42% fat, AIN-93M-AG). The assessments included: body weight, calorie consumption, food efficiency, biochemical analysis of plasma lipids, diameter, total wall thickness, thickness of the tunica mucosa and tunica muscularis, length and width of the intestinal villi, depth of the intestinal crypts and number of goblet cells per mm^-2 (N_A). For the statistical analysis the Student’s t-test was used, considering a P value less than 0.05. The mice in the E group presented greater weight gain (P = 0.028), higher levels of total and LDL cholesterol (P = 0.03 and P = 0.01, respectively), and length of the intestinal villi (P = 0.000). The width of the intestinal villi and the NA of PAS-positive goblet cells presented significantly lower values (P = 0.037 and P = 0.039, respectively) than the C group. The observed changes could be related to the higher demand for fat absorption and to possible alterations in the intestinal microflora and inflammation by action of high-fat diets.     

Experimental study of reproduction in C57Bl/6 and random-bred mice exposed to nonionizing high-frequency radiation

Experimental study of changes in the reproductive function in 10 generations descending from C57Bl/6 and random-bred mice exposed to nonionizing radiation showed a trend to deviation of this function from the normal: the number of newborns in the litter of generations 3–5 was below the normal, which starting from generations 5–6 it gradually increased, approaching the normal. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 141, No. 4, pp. 429–432, April, 2006     

Porphyromonas gingivalis accelerates atherosclerosis in C57BL/6 mice fed a high-fat diet

Objective: Porphyromonas gingivalis has been shown to accelerate atherosclerotic lesion development in atherosclerotic apo E-deficient mice. Here, we investigated whether repeated P. gingivalis injection affected the inflammatory and atherosclerotic responses of C57BL/6 mice fed a high-fat diet (HFD).

Materials and methods: Eight-week-old C57BL/6 mice fed either HFD or a regular chow diet (RD) were inoculated intravenously with P. gingivalis or phosphate-buffered saline three times per week for 10 weeks and sacrificed at 19 weeks of age. Atheromatous lesions in the proximal aorta of each animal were analyzed histomorphometrically, and the serum cytokine and C-reactive protein (CRP) levels were determined.

Results: Long-term HFD feeding as compared to RD feeding led to a slight increase in atheromatous lesions in the aortic sinus as well as increases in the levels of serum monocyte chemoattractant protein 1. Further, P. gingivalis injection significantly enhanced the formation of atherosclerotic plaque, and increased CRP and inflammatory cytokine levels, in mice fed the HFD, although no further increase in LDL was observed.

Conclusion: These results suggest that bacteremia-induced by repeated injection with P. gingivalis accelerates atherosclerosis in normal C57BL/6 mice by initiating inflammation, and is therefore implicated in chronic infection-related pathogenicity.     

Acute exposure to a high-fat diet alters meal patterns and body composition

Weight gain and adiposity are often attributed to the overconsumption of unbalanced, high-fat diets however, the pattern of consumption can also contribute to associated body weight and compositional changes. The present study explored the rapid alterations in meal patterns of normal-weight rats given continuous access to high-fat diet and examined body weight and composition changes compared to chow fed controls. Ten Long-Evans rats were implanted with subcutaneous microchips for meal pattern analysis. Animals were body weight matched and separated into two groups: high-fat or chow fed. Each group was maintained on their assigned diet for nine days and monitored for 22 h each day for meal pattern behavior. Body weight was evaluated every other day, and body composition measures were taken prior and following diet exposure. High-fat fed animals gained more weight and adipose tissue than chow fed controls and displayed a reduced meal frequency and increased meal size. Furthermore, meal size was significantly correlated with the gain of adipose tissue. Together, these results suggest that consumption of a high-fat diet can rapidly alter meal patterns, which in turn contribute to the development of adiposity.     

Sensitivity of immunocompetent cells of DBA/2 and C57Bl/6 mice to cyclophosphamide

T cells were most sensitive to cyclophosphamide in DBA/2 mice, while in C57Bl/6 mice both T and B cells were sensitive. The formation of antibody-producing cells and the production of specific antibodies were delayed in DBA/2 mice immunized after pretreatment with antitumor drug. Accumulation of antibody-producing cells in the spleen was more active in immunized C57Bl/6 mice treated with cyclophosphamide compared to animals not treated with cyclophosphamide.     

podocin和nephrin在高脂饮食C57BL/6J幼鼠肾小球中的表达及意义

目的探讨高脂饮食对幼鼠肾小球裂孔膜蛋白podocin和nephrin表达的影响及意义。方法 36只3周龄雄性C57BL/6J幼鼠随机分为正常饮食组和高脂饮食组,分别给予标准饲料与高脂饲料喂养12周。通过HE和PAS染色观察小鼠肾小球结构的变化;通过免疫组化和免疫印迹技术检测podocin和nephrin蛋白在小鼠肾小球中的表达变化。结果高脂饮食组小鼠出现了肾小囊狭窄以及系膜基质轻度增生等病理改变,且高脂饮食组小鼠肾小球中podocin和nephrin蛋白的表达水平较正常饮食组均显著下调。结论高脂饮食导致裂孔膜蛋白podocin和nephrin低表达,可能是诱发肾小球损伤的原因之一。     

Effect of hyperlipidemia on functional activity of peritoneal macrophages in CBA and C57Bl/6 mice

The effect of experimental hyperlipidemia on functional activity of macrophages was studied in CBA and C57Bl/6 mice resistant and sensitive to the formation of aorta lesions, respectively. Two-month atherogenic diet increased the content of cholesterol in the serum and cells of peritoneal exudate in mice of both strains. In parallel, production of nitrites and 5'-nucleotidase activity in peritoneal macrophages increased, while parameters of phagocytosis, pinocytosis, and NBT test remained unchanged. Changes in the state of macrophages can be explained by increased cholesterol content. The absence of differences in functional activity of macrophages in CBA and C57Bl/6 mice indicates that the observed shifts are insignificant for the development of fatty streaks in the aorta.     

Effect of voluntary wheel exercise on food intake,water intake,and body weight for C57BL/6J mice and mutations which differ in maximal body weight

The relations of voluntary wheel exercise, food intake, water intake, metabolic rate, and body weight were determined for mutant mice (bg, c^J, A^y, and ob) with C57BL/6J genetic background and also for littermate controls. Mutant groups high in body weight (A^y and ob) had lower metabolic rates, were less active, and ate more food than controls. The nonobese mutants (c^J, and bg) had higher metabolic rates than controls, but different behavioral mechanisms for control of body weight during voluntary wheel exercise. Voluntary wheel activity for the albino (c^J) mice was similar to that of controls, but food intake increased proportionally more for albinos than controls. Food intake was similar for beige (bg) mutants compared with controls, but the beige group engaged in less voluntary wheel activity than controls.     

Age- and gender-specific changes of hypocretin immunopositive neurons in C57Bl/6 mice

Loss of neurons or neuronal functions over time has been hypothesized to contribute to the dysregulation of autonomic functions observed in aging. In this study, we evaluated the total number of the hypothalamic hypocretin (orexin) immunopositive neurons in 100, 400, 800 and 1000-day-old male and female C57Bl/6 mice that are commonly used in aging studies in vertebrates. Males had 15–20% more hypocretin immunopositive neurons (HIN) than females at all ages examined. Neuronal number for both sexes was stable in the first 400 days of life, but started declining between 400 and 800 days with rates of approximately 1 neuron/day. The rate of loss doubled in males between 800 and 1000 days of age. The total average number of HIN for males was 2251 ± 139 at 100 days, 2235 ± 112 at 400 days, 1914 ± 81 at 800 days, and 1596 ± 301 at 1000 days. The total average number of HIN for females was 1805 ± 76 at 100 days, 1887 ± 118 at 400 days, and 1521 ± 181 at 800 days. Evaluation of the time-dependent decline in the number of hypocretin immunopositive neurons may help to explain the physiological changes in sleep or energy homeostasis regulation during aging.     

Change in body weight after hormone replacement therapy in postmenopausal women is dependent on basal circulating leptin

Objective: To address the effect of leptin in the modulation of change in body weight after hormone replacement therapy (HRT), we prospectively examined the responses of body weight and serum leptin after estrogen–progestin replacement in postmenopausal women. Patients: Subjects consisted of 63 postmenopausal women aged 54–82 years on HRT for osteoporosis. Design: Thirty three of the subjects received 0.3 mg of conjugated equine estrogen (CEE) (group 1) while 30 were on 0.625 mg of CEE daily (group 2). All subjects also took 5 mg of medrogestone acetate and 750 mg elemental calcium supplement daily. Measurements: Fasting serum leptin was measured by RIA at baseline, 1 and 3 months after treatment. Data were expressed as mean±S.E.M. Results: Serum leptin was highly related to body weight both at baseline (r=0.40, P<0.001) and after 3 months of HRT (r=0.42, P<0.001). When divided the subjects into three equal groups according to baseline leptin levels, it was found that serum leptin significantly decreased in subjects with high baseline leptin at 3 months (−9.4±5.7%, P<0.05) while it increased in subjects whose baseline leptin levels were in the lowest tertile at 1 month (33.2±8.3%, P<0.001) and 3 month (27.8±8.3%, P<0.01). In regards to body weight, those with leptin in the highest tertile demonstrated a reduction of body weight at 3 (−1.9±0.6%, P<0.05) and 12 months (−3.2±0.5%, P<0.05) after HRT while those whose serum leptin levels were in the lowest and middle tertiles did not demonstrate change in body weight. By repeated measured analysis of variance, it was found that the decrease in body weight in subjects with high serum leptin was independent of the doses of estrogen. Conclusion: Postmenopausal hormone replacement does not cause weight gain. However, it results in a small reduction in body weight particularly in subjects with higher basal leptin concentrations.     

Increased sensory neuron apoptotic death 2 weeks after peripheral axotomy in C57BL/6J mice compared to A/J mice

Peripheral nerve transection results in a disconnection of the neuron from its target. As a result, a series of metabolic changes occur in the cell body that may cause neuronal death, mainly by apoptotic mechanisms. Although neurons from neonatal animals are the most susceptible, peripheral, lesion-induced, neuronal loss also occurs in adults, and is particularly evident in mouse sensory neurons. However, differences in genetic background cause particular isogenic strains of mice to react unevenly to peripheral nerve lesion. In this work, we investigated the occurrence of apoptosis as well as the ultrastructural changes in the dorsal root ganglion sensory neurons and satellite cells of C57BL/6J and A/J mice 2 weeks after ipsilateral sciatic nerve transection at the mid-thigh level. C57BL/6J mice displayed a stronger sensory neuron chromatolytic reaction that resulted in an increased loss of neurons when compared with isogenic A/J mice (p<0.01). Additionally, most of the degenerating neurons displayed the classic features of apoptosis. These findings reinforced previous data obtained by the terminal-deoxynucleotidyl transferase nick-end labeling (TUNEL) technique.