Effects of early‐life exposure to Western diet and wheel access on metabolic syndrome profiles in mice bred for high voluntary exercise

Experimental studies manipulating diet and exercise have shown varying effects on metabolic syndrome components in both humans and rodents. To examine the potential interactive effects of diet, exercise and genetic background, we studied mice from four replicate lines bred (52 generations) for high voluntary wheel running (HR lines) and four unselected control lines (C). At weaning, animals were housed for 60 days with or without wheels and fed either a standard chow or Western diet (WD, 42% kcal from fat). Four serial (three juvenile and one adult) blood samples were taken to measure fasting total cholesterol (TC), high‐density lipoprotein cholesterol (HDL‐C), triglycerides and glucose. Western diet was obesogenic for all mice, even after accounting for the amount of wheel running and kilojoules consumed. Western diet significantly raised glucose as well as TC and HDL‐C concentrations. At the level of individual variation (repeatability), there was a modest correlation (r = 0.3–0.5) of blood lipids over time, which was reduced with wheel access and/or WD. Neither genetic selection history nor wheel access had a statistically significant effect on blood lipids. However, HR and C mice had divergent ontogenetic trajectories for body mass and caloric intake. HR mice also had lower adiposity, an effect that was dependent on wheel access. The environmental factors of diet and wheel access had pronounced effects on body mass, food consumption and fasting glucose concentrations, interacting with each other and/or with genetic strain. These data underscore the importance (and often unpredictable nature) of genotype‐by‐environment and environment‐by‐environment interactions when studying body weight regulation.     

C57BL/6J小鼠在构建2型糖尿病模型中体重和非空腹血糖浓度的异常变化

由北京市一实验动物生产单位购入近交系C57BL/6J(B6)和封闭群ICR(3周龄)小鼠,分别以高脂饲料、高脂饲料-3%果糖饮水(实验组)和常规饲料(对照组)喂养6周,实验组腹腔注射链脲佐菌素(STZ,100mg/kg体重),然后以相应饲料继续喂养4周。每周测定小鼠体重,于注射STZ前和注射后每周测定非空腹血糖浓度。研究显示,无论是否补充果糖饮水,B6对照组体重显著高于实验组,而相应周龄的ICR小鼠,实验组体重显著高于对照组。两品系小鼠实验组间体重无差异。注射STZ后,B6实验组血糖浓度均没有达到糖尿病小鼠非空腹血糖浓度的成模标准(11mmol/L),而ICR实验组血糖浓度均达到并超过糖尿病小鼠非空腹血糖浓度的成模标准。研究表明,无论补充果糖与否,ICR小鼠均能成功建模,而B6小鼠建模均失败。因此,ICR小鼠仍是目前应用高脂饲料-STZ联合诱导2型糖尿病模型中经济、有效的候选动物,而B6小鼠在体重和血糖浓度上的异常表现很可能是其遗传背景变化的结果,这尚需进一步研究证实。     

自愿转轮运动对长爪沙鼠身体组成的影响

为研究自愿转轮运动对长爪沙鼠(Meriones unguiculatus)体重的影响,在以前工作的基础上,分析了自愿转轮运动及8周后体重、胴体重和体水,以及心、肝、脾、肺、肾、性腺(睾丸或卵巢)、消化道、腓肠肌、比目鱼肌、肾周脂肪垫和肠系膜脂肪垫等器官及组织的重量变化。结果发现,自愿转轮运动条件下长爪沙鼠胴体湿重、体水和心、肝、脾、肾、腓肠肌、消化道等器官重量增加。自愿转轮运动对比目鱼肌和器官脂肪垫重量的影响存在性别差异。自愿转轮运动使雄性长爪沙鼠器官的脂肪垫重量增加,但雌性降低;对雄性长爪沙鼠比目鱼肌重量没有影响,但雌性增加。以上结果表明,自愿转轮运动促进了长爪沙鼠的体重增长,改变了长爪沙鼠的身体组成。内脏器官和体水重量的增加是体重增加的主要原因。     

Voluntary exercise delays monogenetic obesity and overcomes reproductive dysfunction of the melanocortin-4 receptor knockout mouse

The melanocortin system is involved in hypothalamic regulation of energy homeostasis. The melanocortin-4 receptor (MC4R) has been linked to both obesity and reproductive dysfunction. Deletion of the MC4R from the mouse genome has resulted in phenotypes including adult onset obesity, hyperphagia, and difficulty in reproducing when homozygote parents are bred. Additionally, polymorphisms of the human MC4R have been identified in morbidly obese children and adults. Herein, we have identified that voluntary exercise, provided via the presence of a running wheel, impedes the monogenetic obesity (at 20 weeks of age running wheel housed body weight=31+/-1.8 g versus conventionally housed body weight=41+/-2.3 g, a 25% decrease in body weight p<0.01), hyperphagia (average cumulative food intake is not statistically different than wild type mice housed in running wheel cages), and reproductive dysfunction phenotypes associated with the MC4R knockout mice housed by conventional means. These data demonstrate the novel finding that voluntary exercise at a young age may hinder genetically induced obesity.     

Paternal exercise protects mouse offspring from high-fat-diet-induced type 2 diabetes risk by increasing skeletal muscle insulin signaling

Paternal obesity increases, while paternal exercise decreases, offspring obesity and type 2 diabetes (T2D) risk; however, no studies have determined whether a paternal high-fat (HF) diet and exercise interact to alter offspring body weight (BW), adiposity and T2D risk. Three-week-old male C57BL/6 mice were fed a normal-fat (NF) diet (16% fat) or an HF diet (45% fat) and assigned to either voluntary wheel running exercise or cage activity for 3 months prior to mating with NF-diet-fed dams. After weaning, male offspring were fed an NF or HF diet for an additional 3 months. F1 male mice whose fathers ate an HF diet had decreased % body fat accompanied by decreased gene expression of beige adipocyte marker FGF21. However, paternal HF-diet-induced reductions in F1 offspring % body fat normalized but did not reduce T2D risk. Exercise was protective against paternal HF-diet-induced insulin resistance by increasing the expression of insulin signaling (GLUT4, IRS1 and PI3K) markers in skeletal muscle resulting in normal T2D risk. When fathers were fed an HF diet and exercised, a postnatal HF diet increased beiging (PPARγ). Thus, these findings show that increases in T2D risk in male offspring when the father consumes an HF diet can be normalized when the father also exercises preconception and that this protection may occur by increases in insulin signaling potential within offspring skeletal muscle. Future studies should further determine the physiological mechanism(s) underlying the beneficial effects of exercise through the paternal lineage.     

Architecture of energy balance traits in emerging lines of the Collaborative Cross

The potential utility of the Collaborative Cross (CC) mouse resource was evaluated to better understand complex traits related to energy balance. A primary focus was to examine if genetic diversity in emerging CC lines (pre-CC) would translate into equivalent phenotypic diversity. Second, we mapped quantitative trait loci (QTL) for 15 metabolism- and exercise-related phenotypes in this population. We evaluated metabolic and voluntary exercise traits in 176 pre-CC lines, revealing phenotypic variation often exceeding that seen across the eight founder strains from which the pre-CC was derived. Many phenotypic correlations existing within the founder strains were no longer significant in the pre-CC population, potentially representing reduced linkage disequilibrium (LD) of regions harboring multiple genes with effects on energy balance or disruption of genetic structure of extant inbred strains with substantial shared ancestry. QTL mapping revealed five significant and eight suggestive QTL for body weight (Chr 4, 7.54 Mb; CI 3.32-10.34 Mb; Bwq14), body composition, wheel running (Chr 16, 33.2 Mb; CI 32.5-38.3 Mb), body weight change in response to exercise (1: Chr 6, 77.7Mb; CI 72.2-83.4 Mb and 2: Chr 6, 42.8 Mb; CI 39.4-48.1 Mb), and food intake during exercise (Chr 12, 85.1 Mb; CI 82.9-89.0 Mb). Some QTL overlapped with previously mapped QTL for similar traits, whereas other QTL appear to represent novel loci. These results suggest that the CC will be a powerful, high-precision tool for examining the genetic architecture of complex traits such as those involved in regulation of energy balance.     

Conditioned place preference for cocaine and methylphenidate in female mice from lines selectively bred for high voluntary wheel-running behavior

Behavioral addictions can come in many forms, including overeating, gambling and overexercising. All addictions share a common mechanism involving activation of the natural reward circuit and reinforcement learning, but the extent to which motivation for natural and drug rewards share similar neurogenetic mechanisms remains unknown. A unique mouse genetic model in which four replicate lines of female mice were selectively bred (>76 generations) for high voluntary wheel running (High Runner or HR lines) alongside four non-selected control (C) lines were used to test the hypothesis that high motivation for exercise is associated with greater reward for cocaine (20 mg/kg) and methylphenidate (10 mg/kg) using the conditioned place preference (CPP) test. HR mice run ~three times as many revolutions/day as C mice, but the extent to which they have increased motivation for other rewards is unknown. Both HR and C mice displayed significant CPP for cocaine and methylphenidate, but with no statistical difference between linetypes for either drug. Taken together, results suggest that selective breeding for increased voluntary running has modified the reward circuit in the brain in a way that increases motivation for running without affecting cocaine or methylphenidate reward.     

自愿转轮运动对雄性长爪沙鼠体重和能量代谢的影响

运动是影响动物能量平衡和体重变化的重要因素之一。为研究自愿转轮运动对体重和能量代谢的影响,我们监测了8 周自愿转轮运动过程中,雄性长爪沙鼠的体重、能量摄入、消化率、静止代谢率(RMR) 和非颤抖性产热(NST)的变化,以及8 周后的体脂含量、血清甲状腺激素(T3、T4 )和瘦素(leptin)水平的变化等。结果发现,8 周自愿转轮运动增加了长爪沙鼠的体重和能量摄入以及血清瘦素水平(血清瘦素浓度比对照组高27% ),但对消化率、RMR 和褐色脂肪组织的线粒体蛋白浓度等没有明显影响。尽管体脂含量和血清T₃ 和T₄ 没有显著差异,但运动组体脂含量比对照组高33%,血清T₃ 和T₄ 水平分别比对照组低10% 和38%。血清瘦素浓度与体脂重量呈正相关。因此,自动转轮运动并没有降低动物的体重和体脂含量,但瘦素和甲状腺素在雄性长爪沙鼠能量代谢和能量平衡中的作用尚需进一步确定。     

Do mice bred selectively for high locomotor activity have a greater reliance on lipids to power submaximal aerobic exercise?

Patterns of fuel use during locomotion are determined by exercise intensity and duration, and are remarkably similar across many mammalian taxa. However, as lipids have a high yield of ATP per mole and are stored in large quantities, their use should be favored in endurance-adapted animals. To examine the capacity for alteration or differential regulation of fuel-use patterns, we studied two lines of mice that had been selectively bred for high voluntary wheel running (HR), including one characterized by small hindlimb muscles (HR(mini)) and one without this phenotype (HR(normal)), as well as a nonselected control line. We evaluated: 1) maximal aerobic capacity (Vo(2 max)); 2) whole body fuel use during exercise by indirect calorimetry; 3) cardiac properties; and 4) many factors involved in regulating lipid use. HR mice achieved an increased Vo(2 max) compared with control mice, potentially in part due to HR cardiac capacities for metabolic fuel oxidation and the larger relative heart size of HR(mini) mice. HR mice also exhibited enhanced whole body lipid oxidation rates at 66% Vo(2 max), but HR(mini), HR(normal), and control mice did not differ in the proportional mix of fuels sustaining exercise (% total Vo(2)). However, HR(mini) gastrocnemius muscle had elevated fatty acid translocase (FAT/CD36) sarcolemmal protein and cellular mRNA, fatty acid binding protein (H-FABP) cytosolic protein, peroxisome proliferator-activated receptor (PPAR) α mRNA, and mass-specific activities of citrate synthase, β-hydroxyacyl-CoA dehydrogenase, and hexokinase. Therefore, high-running mouse lines had whole body fuel oxidation rates commensurate with maximal aerobic capacity, despite notable differences in skeletal muscle metabolic phenotypes.     

Voluntary Running in Young Adult Mice Reduces Anxiety-Like Behavior and Increases the Accumulation of Bioactive Lipids in the Cerebral Cortex

Combinatorial therapies using voluntary exercise and diet supplementation with polyunsaturated fatty acids have synergistic effects benefiting brain function and behavior. Here, we assessed the effects of voluntary exercise on anxiety-like behavior and on total FA accumulation within three brain regions: cortex, hippocampus, and cerebellum of running versus sedentary young adult male C57/BL6J mice. The running group was subjected to one month of voluntary exercise in their home cages, while the sedentary group was kept in their home cages without access to a running wheel. Elevated plus maze (EPM), several behavioral postures and two risk assessment behaviors (RABs) were then measured in both animal groups followed immediately by blood samplings for assessment of corticosterone levels. Brains were then dissected for non-targeted lipidomic analysis of selected brain regions using gas chromatography coupled to mass spectrometry (GC/MS). Results showed that mice in the running group, when examined in the EPM, displayed significantly lower anxiety-like behavior, higher exploratory and risky behaviors, compared to sedentary mice. Notably, we found no differences in blood corticosterone levels between the two groups, suggesting that the different EPM and RAB behaviors were not related to reduced physiological stress in the running mice. Lipidomics analysis revealed a region-specific cortical decrease of the saturated FA: palmitate (C16:0) and a concomitant increase of polyunsaturated FA, arachidonic acid (AA, omega 6-C20: 4) and docosahexaenoic acid (DHA, omega 3-C22: 6), in running mice compared to sedentary controls. Finally, we found that running mice, as opposed to sedentary animals, showed significantly enhanced cortical expression of phospholipase A2 (PLA₂) protein, a signaling molecule required in the production of both AA and DHA. In summary, our data support the anxiolytic effects of exercise and provide insights into the molecular processes modulated by exercise that may lead to its beneficial effects on mood.     

Plasma adiponectin is increased in mice selectively bred for high wheel-running activity, but not by wheel running per sé.

Mice selectively bred for high wheel-running activity (S) have decreased fat content compared to mice from randomly bred control (C) lines. We explored whether this difference was associated with alterations in levels of circulating hormones involved in regulation of food intake and energy balance, and whether alterations were caused by the presence of a running wheel. Plasma levels of leptin, adiponectin, and corticosterone as well as body composition were analyzed in male S mice housed with (+) and without (-) access to running wheels at ages of 10 and 18 months. These levels were compared to those found in C+ mice. Plasma corticosterone did not differ among groups. While plasma leptin levels tended to be lower in S+ mice as compared to S- or C+ mice, these differences were largely attributable to differences in fat content. Adiponectin levels were increased in S mice (+60%) compared to C mice, irrespective of wheel access. High levels of this hormone may be a trait co-segregated in mice bred for high wheel-running activity.     

Effects of exercise on weight loss and monocytes in obese mice

Obesity causes innate immune dysfunction, contributing to increased disease risk. Weight loss from a combination of caloric restriction and exercise is the most effective treatment of obesity. We compared forced and voluntary exercise as weight-loss treatments in diet-induced obese (DIO) mice and assessed the effects of weight loss on monocyte concentration and cell-surface expression of Toll-like receptor (TLR) 2, TLR4, CD80, and CD86. DIO CD1 male mice were allocated randomly to 1 of 3 groups (n = 6 per group): voluntary wheel running (VEX); forced treadmill running (FEX); and sedentary (S). A fourth (control) group (CN, n = 6) of nonDIO mice was included also. During the 8-wk weight-loss treatment, all 4 groups consumed a low-fat (10% fat) diet. Nonlethal saphenous vein blood samples collected at baseline, week 4, and week 8 were analyzed by flow cytometry to assess monocyte concentration and functional receptor expression. The VEX and FEX groups lost significantly more body weight (36% and 27%, respectively) over the 8 wk of treatment than did other groups. VEX mice ran 4.4 times more than did FEX animals. VEX mice had higher monocyte concentrations (48% and 58%, respectively) than did the CN and FEX groups. Compared with baseline, week 8 cell-surface expression of TLR2 (22%), TLR4 (33%), and CD86 (18%) was increased in VEX mice. At week 4, CD80 expression was 42% greater for VEX than S mice. The present study confirms that short-term exercise and low-fat diet consumption cause significant weight loss and altered immune profiles.     

Shape‐shift: Semicircular canal morphology responds to selective breeding for increased locomotor activity

Variation in semicircular canal morphology correlates with locomotor agility among species of mammals. An experimental evolutionary mouse model was used to test the hypotheses that semicircular canal morphology (1) evolves in response to selective breeding for increased locomotor activity, (2) exhibits phenotypic plasticity in response to early‐onset chronic exercise, and (3) is unique in individuals possessing the minimuscle phenotype. We examined responses in canal morphology to prolonged wheel access and selection in laboratory mice from four replicate lines bred for high voluntary wheel‐running (HR) and four nonselected control (C) lines. Linear measurements and a suite of 3D landmarks were obtained from 3D reconstructions of μCT‐scanned mouse crania (μCT is microcomputed tomography). Body mass was smaller in HR than C mice and was a significant predictor of both radius of curvature and 3D canal shape. Controlling for body mass, radius of curvature did not differ statistically between HR and C mice, but semicircular canal shape did. Neither chronic wheel access nor minimuscle affected radius of curvature or canal shape These findings suggest that semicircular canal morphology is responsive to evolutionary changes in locomotor behavior, but the pattern of response is potentially different in small‐ versus large‐bodied species.     

Voluntary exercise contributed to an amelioration of abnormal feeding behavior,locomotor activity and ghrelin production concomitantly with a weight reduction in high fat diet-induced obese rats

In the present study, effects of voluntary exercise in an obese animal model were investigated in relation to the rhythm of daily activity and ghrelin production. Male Sprague–Dawley rats were fed either a high fat diet (HFD) or a chow diet (CD) from four to 16 weeks old. They were further subdivided into either an exercise group (HFD-Ex, CD-Ex) with a running wheel for three days of every other week or sedentary group (HFD-Se, CD-Se). At 16 weeks old, marked increases in body weight and visceral fat were observed in the HFD-Se group, together with disrupted rhythms of feeding and locomotor activity. The induction of voluntary exercise brought about an effective reduction of weight and fat, and ameliorated abnormal rhythms of activity and feeding in the HFD-Ex rats. Wheel counts as voluntary exercise was greater in HFD-Ex rats than those in CD-Ex rats. The HFD-obese had exhibited a deterioration of ghrelin production, which was restored by the induction of voluntary exercise. These findings demonstrated that abnormal rhythms of feeding and locomotor activity in HFD-obese rats were restored by infrequent voluntary exercise with a concomitant amelioration of the ghrelin production and weight reduction. Because ghrelin is related to food anticipatory activity, it is plausible that ghrelin participates in the circadian rhythm of daily activity including eating behavior. A beneficial effect of voluntary exercise has now been confirmed in terms of the amelioration of the daily rhythms in eating behavior and physical activity in an animal model of obesity.     

Adiponectin is regulated differently by chronic exercise than by weight-matched food restriction in hyperphagic and obese OLETF rats

This study was intended to investigate the effects of chronic exercise on blood adiponectin level. Male Otsuka Long Evans Tokushima Fatty (OLETF) rats (26 weeks old) were divided to undergo either regular 12-week wheel running exercise (EX) or to have food restriction (FR) that resulted in body weight reduction similar to that in EX. Both EX and FR induced similar reductions in body weight, abdominal fat volume and plasma leptin concentration compared with ad libitum control. At the end of the study, although plasma adiponectin level was increased in FR, the adiponectin level did not change in EX. Plasma testosterone level was higher in EX than in either of the other two groups. A significant inverse relationship existed between plasma levels of adiponectin and testosterone for all groups. Our results suggested that 12-week voluntary wheel running exercise induces different effects on plasma adiponectin level than does food restriction, despite similar reduction in body weight, fat tissue mass and plasma leptin concentration. We speculate that the elevated plasma testosterone concentration might offset any hyperadiponectinemic effect of body weight and fat volume reduction in exercising rats.     

Evolution of hindlimb bone dimensions and muscle masses in house mice selectively bred for high voluntary wheel‐running behavior

We have used selective breeding with house mice to study coadaptation of morphology and physiology with the evolution of high daily levels of voluntary exercise. Here, we compared hindlimb bones and muscle masses from the 11th generation of four replicate High Runner (HR) lines of house mice bred for high levels of voluntary wheel running with four non‐selected control (C) lines. Mass, length, diameter, and depth of the femur, tibia‐fibula, and metatarsal bones, as well as masses of gastrocnemius and quadriceps muscles, were compared by analysis of covariance with body mass or body length as the covariate. Mice from HR lines had relatively wider distal femora and deeper proximal tibiae, suggesting larger knee surface areas, and larger femoral heads. Sex differences in bone dimensions were also evident, with males having thicker and shorter hindlimb bones when compared with females. Several interactions between sex, linetype, and/or body mass were observed, and analyses split by sex revealed several cases of sex‐specific responses to selection. A subset of the HR mice in two of the four HR lines expressed the mini‐muscle phenotype, characterized mainly by an ～50% reduction in hindlimb muscle mass, caused by a Mendelian recessive mutation, and known to have been under positive selection in the HR lines. Mini‐muscle individuals had elongated distal elements, lighter and thinner hindlimb bones, altered 3rd trochanter muscle insertion positions, and thicker tibia‐fibula distal widths. Finally, several differences in levels of directional or fluctuating asymmetry in bone dimensions were observed between HR and C, mini‐ and normal‐muscled mice, and the sexes. This study demonstrates that skeletal dimensions and muscle masses can evolve rapidly in response to directional selection on locomotor behavior.     

The M16 Mouse: An Outbred Animal Model of Early Onset Polygenic Obesity and Diabesity

Objective: To characterize the phenotypic consequences of long‐term selective breeding for rapid weight gain, with an emphasis on obesity and obesity‐induced diabetes (diabesity). Research Methods and Procedures: M16 is the result of long‐term selection for 3‐ to 6‐week weight gain from an ICR base population. Experiment 1 characterized males from both lines for body weights (3, 6, and 8 weeks), feed (4 to 8 weeks) and H₂O (6 to 8 weeks) consumption, and heat loss, body composition, and levels of several plasma proteins at 8 weeks of age. Experiment 2 characterized differences between lines for both sexes at three ages (6, 8, and 16 weeks) and fed two diets (high and normal fat). Body weight, composition, blood glucose, and plasma insulin and leptin levels were evaluated after an 8‐hour fast. Results: At all ages measured, M16 mice were heavier, fatter, hyperphagic, hyperinsulinemic, and hyperleptinemic relative to ICR. M16 males and females were hyperglycemic relative to ICR, with 56% and 22% higher fasted blood glucose levels at 8 weeks of age. Discussion: M16 mice represent an outbred animal model to facilitate gene discovery and pathway regulation controlling early onset polygenic obesity and type 2 diabetic phenotypes. Phenotypes prevalent in the M16 model, with obesity and diabesity exhibited at a young age, closely mirror current trends in human populations.     

Baseline and stress-induced plasma corticosterone concentrations of mice selectively bred for high voluntary wheel running

The hypothalamic-pituitary-adrenal (HPA) axis is important in regulating energy metabolism and in mediating responses to stressors, including increasing energy availability during physical exercise. In addition, glucocorticoids act directly on the central nervous system and influence behavior, including locomotor activity. To explore potential changes in the HPA axis as animals evolve higher voluntary activity levels, we characterized plasma corticosterone (CORT) concentrations and adrenal mass in four replicate lines of house mice that had been selectively bred for high voluntary wheel running (HR lines) for 34 generations and in four nonselected control (C) lines. We determined CORT concentrations under baseline conditions and immediately after exposure to a novel stressor (40 min of physical restraint) in mice that were housed without access to wheels. Resting daytime CORT concentrations were approximately twice as high in HR as in C mice for both sexes. Physical restraint increased CORT to similar concentrations in HR and C mice; consequently, the proportional response to restraint was smaller in HR than in C animals. Adrenal mass did not significantly differ between HR and C mice. Females had significantly higher baseline and postrestraint CORT concentrations and significantly larger adrenal glands than males in both HR and C lines. Replicate lines showed significant variation in body mass, length, baseline CORT concentrations, and postrestraint CORT concentrations in one or both sexes. Among lines, both body mass and length were significantly negatively correlated with baseline CORT concentrations, suggesting that CORT suppresses growth. Our results suggest that selection for increased locomotor activity has caused correlated changes in the HPA axis, resulting in higher baseline CORT concentrations and, possibly, reduced stress responsiveness and a lower growth rate.     

Comparison of the obesity phenotypes related to monosodium glutamate effect on arcuate nucleus and/or the high fat diet feeding in C57BL/6 and NMRI mice

In this study, susceptibility of inbred C57BL/6 and outbred NMRI mice to monosodium glutamate (MSG) obesity or diet-induced obesity (DIO) was compared in terms of food intake, body weight, adiposity as well as leptin, insulin and glucose levels. MSG obesity is an early-onset obesity resulting from MSG-induced lesions in arcuate nucleus to neonatal mice. Both male and female C57BL/6 and NMRI mice with MSG obesity did not differ in body weight from their lean controls, but had dramatically increased fat to body weight ratio. All MSG obese mice developed severe hyperleptinemia, more remarkable in females, but only NMRI male mice showed massive hyperinsulinemia and an extremely high HOMA index that pointed to development of insulin resistance. Diet-induced obesity is a late-onset obesity; it developed during 16-week-long feeding with high-fat diet containing 60 % calories as fat. Inbred C57BL/6 mice, which are frequently used in DIO studies, both male and female, had significantly increased fat to body weight ratio and leptin and glucose levels compared with their appropriate lean controls, but only female C57BL/6 mice had also significantly elevated body weight and insulin level. NMRI mice were less prone to DIO than C57BL/6 ones and did not show significant changes in metabolic parameters after feeding with high-fat diet.