FEATURES OF THE VARIATIVE MORPHOLOGY OF THE MANDIBULAR SECOND MOLAR USING CONE-BEAM COMPUTED TOMOGRAPHY IMAGING.

OBJECTIVE: The aim: To characterize the variations in the anatomical structure of the second lower molar. PATIENTS AND METHODS: Materials and methods: In order to determine the topography of the roots and root canals of the mandibular second molar, modern imaging methods were used: orthopan¬tomography and cone-beam computed tomography. RESULTS: Case report: During the analysis of the orthopantomogram of the patient, the three-root morphology of the root system of 37 teeth was revealed. That is, three roots were clearly visualized. After detecting an atypical shape of the root system of the mandibular second molar in the panoramic image, the patient was offered to perform cone-beam computed tomography (CPCT) for diagnostic purposes. Analysis by cone-beam computed tomography showed the presence of four mature roots of normal length, which were arranged in the shape of a diamond. CONCLUSION: Conclusions: The four-root configuration is considered a rare form for mandibular molars, but it should be considered in endodontic interventions and, if possible, in the planning of such interventions, use cone-beam computed tomography.

CHARACTERISTICS OF METAL ALLOYS PROPERTIES FOR DENTAL CASTING AFTER THEIR REPEATED REMELTING.

OBJECTIVE: The aim: To study clinical and experimental substantiation of the possibility of using cobalt-chromium and nickel-chromium alloys after repeated remelting for non-removable one-piece prosthetics. PATIENTS AND METHODS: Materials and methods: Experimental studies of Remanium GM 700 and Remanium CSe dental alloys have been carried out. To study the physical and mechanical properties of alloys, samples were obtained by sequential six-fold remelting in a Tiegelschleuder TS casting dental unit manufactured by Degussa. All samples were subjected to chemical analysis and metallographic studies by methods generally known in metallurgy, which included studies of microhardness, elasticity, tensile deformation, bending deformation and alloy structure after repeated remelting. RESULTS: Results: Thus, the obtained results of the chemical, physicomechanical and structural properties of the remelts indicate that the Remanium GM 700 and Remanium СSe alloys can be reused many times for the manufacture of one-piece orthopedic structures in that they are identical with certified alloys. CONCLUSION: Conclusions: In terms of structure, qualitative and quantitative composition of elements, physical and technological properties, the Remanium GM 700 and Remanium CSe alloys have been repeatedly remelted meet the requirements of materials used in biologically active environments of the patient's body. High-quality and cost-effective remelted multiple times Remanium GM 700 and Remanium CSe alloys can be recommended for use in practical prosthetic dentistry six times.

COMPARATIVE EVALUATION OF HISTOTOXICITY INDICATORS OF METAL ALLOYS FOR THE MANUFACTURE OF METAL CERAMIC DENTAL CONSTRUCTIONS.

OBJECTIVE: The aim: To carry out a comparative assessment of metal alloys for the manufacture of metal-ceramic constructions of dentures by determining the indicator of their histotoxicity. PATIENTS AND METHODS: Materials and methods: To identify the effect of metal alloys on cobalt and nickel bases on the tissue of organism, we carried out an experimental-morphological study of standard samples of metal alloys "Shot-alloy", "Remanium-2000", "Cerium", "Dent-NCB", "Cellite-N". RESULTS: Results: A careful histological analysis of the capsules formed around the metal alloy samples during two periods of the experiment showed that the healing time of the subcutaneous tissue was not the same. The most complete healing, that is, the formation of mature fibrous connective tissue, occurred during the implantation of the cobaltbased alloy "Remanium-2000" and the capsule formed at the end of the experiment around the implanted sample from the "Shot-alloy" alloy, and during the implantation of the "Cerium" alloy, healing the wound surface and the formation of a connective tissue capsule occurs fully than in previous cases. CONCLUSION: Conclusions: The analysis of the performed experiment testifies in favor of the point of view that the speed and quality of healing of damaged subcutaneous tissue upon the introduction of implanted research alloys depend largely on the individual chemical components that make up the alloys, or on their combination.

MORPHOLOGICAL FEATURES OF THE UTERUS IN WOMEN AT DIFFERENT TIME INTERVALS OF THE POSTMORTEM PERIOD AS DIAGNOSTIC CRITERIA FOR ESTABLISHING THE POSTMORTEM INTERVAL.

OBJECTIVE: The aim is to identify the morphological features of the uterus layers in women at different time intervals of the postmortem period as diagnostic criteria for establishing the postmortem interval. PATIENTS AND METHODS: Materials and methods: In the study we used surgical and autopsy material - uterine tissue fragments. All materials were divided into two groups. The 1st group (G 1) included surgical material from women (n=6) who underwent removal of the uterus, or uterus with the appendages due to leiomyoma, uterine prolapse. The 2nd group (G 2) included autopsy material from 42 women with known causes of death and postmortem period (from 24 to 48 hours - 6 cases, from 49 to 72 hours - 7 cases, from 73 to 96 hours - 8 cases, from 97 to 120 hours - 6 cases, from 121 to 144 hours - 8 cases, more than 144 hours - 7 cases). Histological and immunohistochemical study methods were used. RESULTS: Results: A comprehensive morphological study of the women uterus revealed a time-dependent increase of postmortem changes in this organ linked with the increase of postmortem period. In cases of postmortem period duration up to 144 hours, the structural elements of the uterine layers were identified. In cases where the duration of the postmortem period was more than 145 hours, microscopically the uterus was represented by eosinophilic fibrous or dusty masses, the histogenesis of which could not be determined. The processes of autolysis occurred more intensely and faster in the mucous membrane of the uterus, in comparison with the muscular and serous membranes, and in the vessels - in their inner membrane, in comparison with the middle and outer membranes. Autolytic changes in the muscular membrane of the uterus and vascular walls occurred more intensely in muscle fibers compared to connective tissue fibers. CONCLUSION: Conclusions: The histological and immunohistochemical features of the women uterus at different postmortem periods have a certain forensic medical significance and can be used for establishing the postmortem interval.

EPIDEMIOLOGICAL INDICATORS OF DENTAL MORBIDITY OF CHILDREN AS AN INDICATOR OF ADVERSE ENVIRONMENTAL INFLUENCE.

OBJECTIVE: The aim: Is to study the ecological and hygienic situation in the living area of 6-year-old children in terms of drinking water (micro- and macroelements), to identify its relationship with the state of mineral metabolism in children's mouths, prevalence and intensity of temporary and permanent caries. PATIENTS AND METHODS: Materials and methods:Clinical and laboratory studies were to study the objective condition of the teeth -intensity of dental caries according to the recommendations of the WHO and the method of T.F. Vinogradova. The hygienic condition of the oral cavity was determined by the indices Silness-Loe, Stallard. RESULTS: Results: The results of our studies have shown that the proposed therapeutic and prophylactic complex, which includes drugs of endogenous (Vitafluor) and exogenous use (osteovitis, deep fluoridation, toothpastes "Splat junior" and "Lacalut fluor"), improves the hygienic state of the oral cavity, increases mineralizing the potential of the oral fluid and, as a result, helps to reduce the intensity of dental caries in children. CONCLUSION: Conclusions: The data obtained indicated a high caries prophylactic efficacy of the proposed therapeutic and prophylactic complex for 6-year-old children living in the zone of hypophtorosis.

MINERALIZATION OF TEETH ENAMEL AFTER ERUPTION.

OBJECTIVE: The aim: The paper was aimed at the study of the processes of mineralization of the enamel of the permanent tooth after its eruption. PATIENTS AND METHODS: Materials and methods: To study the structure of the enamel of permanent teeth has been carried out using light and electron microscopy. The study of the process of the development of the primordia of the permanent teeth involved 10 culled puppies of 30-40 days of age. Microscopic, electron microscopic, immunohistochemical methods of research have been used to study the processes of histogenesis. RESULTS: Results: The studies show that in the postnatal period, the formation of the crown, externally covered with cuticular epithelium, marks the formation of the primordium of the permanent tooth at the follicle stage. After eruption of a tooth, different parts of its crown have three individual structural and functional barriers to enamel biomineralization. The first one is provided by the cuticular epithelium of the pitted areas of the crown, which ensures filtering of the salivary fluid from the protein deposit in the form of a pellicle. The second barrier is defined on the lateral and cuspidate surfaces of the enamel, where the cuticle is erased or poorly expressed. The third structural and functional barrier of enamel biomineralization is located in the cervical portion of teeth of different classes. CONCLUSION: Conclusions: Different areas of the enamel in the tooth crown have specific filtration barriers, which can be distinguished as follows: pit-and-fissure-and-groove, cuspidateand-approximal, and cervical barriers. The cuticle is poorly expressed or totally absent on the cusps of the tooth crowns in contrast to pitted areas.

VASCULAR ANOMALIES IN NEWBORNS: CLINICAL PRESENTATION, COMPLICATIONS, AND PECULIARITIES OF THERAPY.

OBJECTIVE: The aim: To analyze cases of vascular anomalies in newborns retrospectively to study their main clinical signs and to determine indications for urgent treatment. PATIENTS AND METHODS: Materials and methods: A retrospective review of 281 pediatric vascular anomalies diagnosed between 2011 and 2019 was performed. The results of clinical examination, prenatal history, laboratory, sonography, and radiological data were evaluated. RESULTS: Results: Clinical manifestations in the newborn period documented in 170 (60.5%) patients, anomalies were visualized prenatally in 8.9% cases. Five newborns with head and neck LMs required urgent treatment, which amounted 7.9% of all newborns with LMs. The indication for urgent surgery was acute respiratory failure. Partial malformation resection with tracheostomy was performed to those patients, along with intraoperative injection of sclerotherapeutic agents and argon coagulation of residual malformation tissues. EXIT procedure was performed in one case. No correlation (p=0.2) was found between the number of skin lesions and the severity of liver lesions in children with multifocal hepatic hemangiomas, congestive cardiac failure suddenly occurs in one patient in the third week of life. Two newborns with diffuse hepatic hamangioma were manifested right after the birth with clinical signs of liver failure, hypothyreosis, and cardiac failure. Short courses of corticosteroids performed in 7 patients with KHE and Kasabach-Merritte fenomemn for thrombocytopenia correction. CONCLUSION: Conclusions: Clinical signs of vascular anomalies in neonatal period were seen in 57.5% children with vascular anomalies, and only 2.9% of them required treatment. Treatment itself is advantageous only in cases when life-threatening complications develop, such as airways obstruction, cardiac and/or liver failure, thrombocytopenia.

WEAR RESISTANCE OF DENTAL MATERIALS WHICH ARE USED FOR ANTERIOR TEETH RESTORATIONS.

OBJECTIVE: The aim of this study was to compare the wear resistance of such restorative materials as composite resin, feldspathic ceramic, leucite glass ceramic with intact enamel and to draw an analogy with some similar researches. PATIENTS AND METHODS: Materials and methods: In this research 20 extracted human teeth (maxillary incisors) without fillings and carious cavities were used as samples. All samples were disinfected and stored in saline in order to prevent dehydration. Teeth roots were cut off for the measure of fixation on an organic glass plate using chemically polymerizable resin. If necessary, the teeth were also cut on their lateral sides in order to give them equal size. The samples were placed in a frame-holder, located on the lever of the machine MI-2, which determines abrasion resistance under slipping. RESULTS: Results: The research has revealed that the average wear resistance of natural teeth was 122,67±4.9 J/mm3 (Tab 1). The archived result overcomes dental composite resin twice more (62.8±1.21 J/mm3), feldspathic ceramic 6.5 times more (16.32±1.2 J/mm3) and leucite ceramic over the half (73.79±3.12 J/mm3). CONCLUSION: Conclusion: Thus, according to this performed research and the analysis of the relative literature sources it can be stated that dental composite resin and leucite ceramics may be proposed as the materials of choice for anterior restoration of teeth. They have shown the good wear resistance and tolerance to antagonizing natural teeth.

The intensity of chronic catarrhal gingivitis in children depending on the age.

OBJECTIVE: The aim: To determine the degree of severity of the inflammatory process in periodontal tissues of children living in different ecological conditions. PATIENTS AND METHODS: Materials and methods: With the purpose of estimation of the condition of periodontal tissues the epidemiology examination of 642 children that live on territory with the high level of pollution and natural deficit of iodine and fluorine was conducted. RESULTS: Results: The study found that the increase of age of examined children causes the decrease of percentage of easy degree of severity of chronic catarrhal gingivitis, giving way to the advanced forms of the disease, and this process was more pronounced in children living in ecologically polluted region. In children-inhabitants of ecologically clean region easy degree of severity of chronic catarrhal gingivitis met more often than their peers living in environmentally polluted region. At the same time, average and heavy degree of severity of chronic catarrhal gingivitis in children living in ecologically contaminated region met more often than their peers, inhabitants of ecologically clean region. CONCLUSION: Conclusions. It was found that with increasing age of the examined children decreases the percentage of chronic catarrhal gingivitis of moderate severity.

Features of the course of enamel biomineralization processes in various anatomical areas of the tooth.

OBJECTIVE: The aim: To establish the features of the structural organization of enamel in various anatomical areas of the tooth and determine their influence on the characteristics of the course of biomineralization processes. PATIENTS AND METHODS: Materials and methods: The study of the structural features of enamel and dentin was performed on thin sections of various groups of teeth. Then morphological, histochemical and electron microscopic examination methods were used. RESULTS: Results: The study found that there are three structural and functional barriers to biomineralization of enamel, which are located in different anatomical areas of the tooth crown. Each of them has both general and specific features. Enamel biomineralization is a continuous process of exchange of calcium ions, donor of which is brushite. The stepwise process of biomineralization turns the latter into calcium octaphosphate, which then turns into hydroxyapatite. The latter, when destroyed by carbon dioxide, forms carboxyapatite. CONCLUSION: Conclusions: In the result of conducted study was established peculiarities of enamel mineralization processes in different anatomical parts of tooth.

DENTAL CROWN BIOMINERALIZATION DURING ITS HISTOGENESIS.

OBJECTIVE: The aim: Thepaper wasaimedat thestudyof thebiomineralization processesofa permanentdental crown in thepostnatal period of histogenesis. PATIENTS AND METHODS: Materials and methods: The study involved 30 culled puppies aged 30-40 days. To study the histogenesis of the germs of the permanent tooth from the cuticular epithelium in the postnatal period microscopic, electron microscopic, immunohistochemical methods of study have been used. RESULTS: Results: The studies show that in the postnatal period, the maturation of the germ of a permanent tooth starts with the synthesis of cells of the cuticular epithelium of the organic stroma, capable of subsequent mineralization. Differentiation of the proameloblasts, located on the surface of the dental papillary mesenchyma, at the early stages of histogenesis, is strongly associated with the appearance of a specific protein taftelin. Origination of secretory ameloblasts, which produce the protein enamelin, triggers the process of secondary biomineralization of the enamel. The terminal processes of the secretory ameloblasts produce the protein in the form of layers that overlap each other at a certain angle. Such layering of the structures of enamel and dentin contributes to the S-shaped maturation of the hard tooth tissues, strengthening them considerably. At the follicle stage, maturation of the dental crown, coated with cuticular epithelium, occurs. Invaginations of the cuticular epithelium form a characteristic topography of the dental crown, and enamel projections are further formed by the ameloblasts. Epitheliocytes of the inner layer of the enamel organ have desmosomal connections that allow the filtration of the salivary fluid at the stage of the enamel trophism. CONCLUSION: Conclusions: The findings of the study suggest that, normally, due to the cuticular epithelium, filtration of the salivary fluid occurs with protein deposition on it and subsequent infiltration of the calcium salts into the subjacent enamel.

Neonatal 6-hydroxydopamine lesions of the frontal cortex in rats: persisting effects on locomotor activity, learning and nicotine self-administration.

Dopaminergic innervation of the frontal cortex in adults is important for a variety of cognitive functions and behavioral control. However, the role of frontal cortical dopaminergic innervation for neurobehavioral development has received little attention. In the current study, rats were given dopaminergic lesions in the frontal cortex with local micro-infusions of 6-hydroxydopamine (6-OHDA) at 1 week of age. The long-term behavioral effects of neonatal frontal cortical 6-OHDA lesions were assessed in a series of tests of locomotor activity, spatial learning and memory, and i.v. nicotine self-administration. In addition, neurochemical indices were assessed with tissue homogenization and HPLC in the frontal cortex, striatum, and nucleus accumbens of neonatal and adult rats after neonatal 6-OHDA lesions. In neonatal rats, frontal 6-OHDA lesions as intended caused a significant reduction in frontal cortical dopamine without effects on frontal cortical 5-HT and norepinephrine. The frontal cortical dopamine depletion increased 5-HT and norepinephrine levels in the nucleus accumbens. Locomotor activity assessment during adulthood in the figure-8 maze showed that lesioned male rats were hyperactive relative to sham-lesioned males. Locomotor activity of female rats was not significantly affected by the neonatal frontal 6-OHDA lesion. Learning and memory in the radial-arm maze was also affected by neonatal frontal 6-OHDA lesions. There was a general trend toward impaired performance in early maze acquisition and a paradoxical improvement at the end of cognitive testing. Nicotine self-administration showed significant lesion x sex interactions. The sex difference in nicotine self-administration with females self-administering significantly more nicotine than males was reversed by neonatal 6-OHDA frontal cortical lesions. Neurochemical studies in adult rats showed that frontal cortical dopamine and DOPAC levels significantly correlated with nicotine self-administration in the 6-OHDA-lesioned animals but not in the controls. Frontal cortical 5-HT and 5HIAA showed inverse correlations with nicotine self-administration in the 6-OHDA-lesioned animals but not in the controls. These results show that interfering with normal dopamine innervation of the frontal cortex during early postnatal development has persisting behavioral effects, which are sex-specific.

[HLA genomic tissue typing in myasthenic patients with rheumatoid arthritis]. / A humán leukocytaantigének molekuláris genetikai vizsgálata myastheniás elózmény után kialakult rheumatoid arthritisben.

In a 36 years old male and a 56 years old female myasthenic patient thymectomy was performed several years ago. In the male patient 5, and in the female patient 7 years after the operation rheumatoid arthritis developed. The rheumatoid arthritis in the male patient was seropositive with marginal erosions in the carpometacarpal and in the tarsometatarsal joints. The female patient had no joint destruction and was seronegative as well. The female patient had also an abnormal ratio between the separated CD4 and CD8 T-cells. The major histocompatibility complex determined by the serological methods revealed a haplotype of HLA-A1-B8-D3-DQ2, which is typically due to the myasthenic disease. In the female patient the molecular analysis of the HLA-D region showed a HLA-DRB1* 0401 allele, which is frequently associated with rheumatoid arthritis. The male patient had no allelic variant which could be related to his chronic disabilitating joint disease.

Diazoxide restores beta3-adrenergic receptor function in diet-induced obesity and diabetes.

We previously demonstrated that the expression and function of the adipocyte-specific beta3-adrenergic receptor (beta3AR) are significantly depressed in single gene and diet-induced rodent models of obesity. Furthermore, these models are relatively unresponsive to the anti-obesity effects of beta3AR agonists. Because all of these models are hyperinsulinemic, we hypothesized that hyperinsulinemia could be responsible for this abnormality in beta3AR function. The goal of this study was to determine whether lowering insulin with the K-ATP channel agonist, diazoxide (Dz) would reverse the depressed expression and function of the beta3AR found in a model of diet-induced diabetes and obesity in C57BL/6J (B6) mice. B6 male mice were placed on either high fat (HF) or low fat experimental diets. After 4 weeks, HF-fed mice were assigned to a group: HF or HF containing disodium (R,R)-5- [2-( [2-(3-chlorophenyl)-2-hydroxyethyl]-amino]propyl-1,3-benzodioxole-2,2-di carboxylate (CL; 0.001%, wt/wt), Dz (0.32%, wt/wt), or their combination (CLDz). Dz animals exhibited significantly reduced plasma insulin levels as well as increased 3pAR expression and agonist-stimulated adenylyl cyclase activity in adipocytes. CLDz was more effective in reducing percent body fat, lowering nonesterified fatty acids, improving glucose tolerance, and reducing feed efficiency than either treatment alone.

Transient effects of long-term leptin supplementation in the prevention of diet-induced obesity in mice.

Low plasma leptin levels have been shown to be associated with the development of obesity in mice as well as in humans. The present study was undertaken to determine if raising plasma leptin levels of obesity-prone C57BL/6J (B6) mice to those seen in obesity-resistant A/J mice would prevent the development of diet-induced obesity. Four-week-old B6 (n = 40) and A/J (n = 10) male mice were weaned onto a low-fat (11% kcal) diet. When the animals weighed 20 g, their diets were changed to a high-fat (HF) diet (58% kcal), and a continuous infusion of leptin (0.4 mg x kg(-1) x day(-1)) or phosphate-buffered saline (control) was started using Alzet minipumps. The A/J mice were not treated but were included to monitor the efficacy of the minipumps in raising plasma leptin in B6 mice. The mice were followed for 12 weeks. Chronic treatment with leptin for 4 weeks raised plasma levels in B6 mice to that of A/J mice. Plasma leptin in B6 control mice remained significantly lower than A/J mice through week 4. By week 8, leptin levels in the B6 control group had risen and were similar to A/J mice. Although there were significant weight differences between B6 treated and B6 control groups for 2-3 weeks after pump implantation, these differences were transient. Ultimately, there were no weight differences between the B6 treated and B6 control groups. There were no differences in plasma glucose between B6 treated and control groups. Plasma insulin values were also not different between the 2 groups. There was no effect of leptin supplementation on locomotor activity or food intake in B6 mice. In summary, this study demonstrates that leptin supplementation in animals that show low plasma leptin levels in response to fat feeding may slow but does not prevent the subsequent development of diet-induced obesity.

Induction of enlarged intestinal lymphoid aggregates during acute glutathione depletion in a murine model.

Glutathione is a nonenzymatic antioxidant synthesized by most animal cells and is depleted in inflammatory bowel disease. The effects of glutathione depletion on intestinal histology and inhibitory neurochemicals was examined in a mouse model. Glutathione depletion in A/J mice involved inhibition of gamma-glutamylcysteine synthetase using L-buthionine-(S,R)-sulfoximine (BSO) for 10 days. Ileum and colon were obtained from saline-control mice, BSO-treated mice, and BSO-treated mice receiving ascorbate or glutathione monoethylester. Glutathione, lipid peroxides, and nicotineamide adenine dinucleotide phosphate diaphorase activity were measured by colorimetric assays. Vasoactive intestinal peptide was measured by radioimmunoassay. Glutathione depletion induced enlargement of mucosal-submucosal lymphoid aggregates without germinal centers in ileum and colon. These aggregates were prevented by supplementation with glutathione monoethylester but not ascorbate. Tissue levels of inhibitory neurochemicals were unchanged. Depletion of glutathione appears to induce enlarged lymphoid aggregates by recruitment of lymphocytes from the peripheral circulation. A component of the inflammation that develops in inflammatory bowel disease could be related to depletion of tissue levels of glutathione.

Synthesis and biological activity of 4-alkoxy chalcones: potential hydrophobic modulators of P-glycoprotein-mediated multidrug resistance.

A series of 4-alkoxy-2',4',6'-trihydroxychalcones have been synthesized and evaluated for their ability to inhibit P-glycoprotein-mediated multidrug resistance (MDR) by direct binding to a purified protein domain containing an ATP-binding site and a modulator-interacting region. The introduction of hydrophobic alkoxy groups at position 4 led to much more active compounds as compared to the parent chalcone. The binding affinity increased as a function of the chain length, up to the octyloxy derivative for which a K(D) of 20 nM was obtained.

Differential effects of fat and sucrose on body composition in A/J and C57BL/6 mice.

The C57BL/6 (B6) mouse is more sensitive to the effects of a high-fat diet than the A/J strain. The B6 mouse develops severe obesity, hyperglycemia, and hyperinsulinemia when fed this dietary regimen. This study was conducted to determine the effects of dietary fat and sucrose concentrations on body composition and intestinal sucrase (EC 3.2.1.48) and maltase (EC 3.2.1.20) activity in these two mouse strains. High-fat diets, regardless of sucrose content, resulted in significant weight gain, higher body fat, and lower body protein and water content in both strains of mice. The shift toward higher body fat and lower protein and water content was far greater in the B6 strain. Low-fat, high-sucrose diets resulted in lower body weight in both strains, as well as significantly greater body protein content in B6 mice. Analysis of intestinal sucrase showed that the enzyme was less active in B6 mice when the diet was high in sucrose. Both sucrase and maltase had lower activity in the presence of high dietary fat in both mouse strains. The percent reduction of intestinal enzyme activity due to dietary fat was similar in both strains. The B6 mouse exhibits disproportionate weight gain and altered body composition on a high-fat diet. This coupled with the reduced body weight and increased body protein on a low-fat, high-sucrose diet suggests that factors-relative to fat metabolism rather than sucrose metabolism are responsible for obesity.

Reversal of diet-induced obesity and diabetes in C57BL/6J mice.

We have previously shown that C57BL/6J (B6) mice develop severe obesity and diabetes if weaned onto high-fat diets, whereas A/J mice tend to be obesity and diabetes-resistant. The purpose of this study was to determine if obesity and diabetes in the B6 mouse could be completely reversed by reducing dietary fat content. After 4 months, both strains consumed more calories on a high-fat diet than on a low-fat diet, and both strains showed a higher feed efficiency (FE=weight gained/calories consumed) on the high-fat diet versus the low-fat diet. However, relative to A/J mice, B6 mice demonstrated a significantly higher FE on the high-fat diet. Hyperglycemia, hyperinsulinemia, and increased adiposity were apparent in B6 mice after 4 months on the high-fat diet regardless of whether the diet was begun at weaning or 4 months later. Correlational analyses showed that adiposity was strongly related to both insulin and glucose levels in B6 mice, but only moderately related to insulin levels in A/J mice. In obese B6 mice that were switched to a low-fat diet, obesity and diabetes were completely reversed. Adiposity, fasting glucose, and fasting insulin values in these mice were equivalent to those in B6 mice of the same age that had spent 8 months on the low-fat diet. In summary, our data show that in the B6 mouse the severity of diabetes is a direct function of obesity and diabetes is completely reversible by reducing dietary fat.

Diet-induced changes in uncoupling proteins in obesity-prone and obesity-resistant strains of mice.

Uncoupling protein 2 (UCP2) maps to a region on distal mouse chromosome 7 that has been linked to the phenotypes of obesity and type II diabetes. We recently reported that UCP2 expression is increased by high fat feeding in adipose tissue of the A/J strain of mice, which is resistant to the development of dietary obesity. More recently, a third UCP (UCP3) was identified, which is expressed largely in skeletal muscle and brown adipose tissue. The UCP2 and UCP3 genes are located adjacent to one another on mouse chromosome 7. Thus, the roles of these UCPs in both metabolic efficiency and the linkage to obesity and diabetes syndromes is unclear. For this reason, we examined the expression of UCP2 and UCP3 in white adipose tissue and interscapular brown adipose tissue and in gastrocnemius/soleus muscle preparations from the obesity-resistant A/J and C57BL/KsJ (KsJ) strains and the obesity-prone C57BL/6J (B6) mouse strain. In both KsJ and A/J mice, UCP2 expression in white fat was increased approximately 2-fold in response to 2 weeks of a high fat diet, but there was no effect of diet on UCP2 levels in B6 mice. In skeletal muscle and in brown fat, neither UCP2 nor UCP3 expression was affected by diet in A/J, B6, or KsJ mice. However, in brown fat, we observed a 2-3-fold increase in the expression of UCP1 in response to dietary fat challenge, which may be related to diet-induced elevations in plasma leptin levels. Together, these results indicate that the consumption of a high fat diet selectively regulates UCP2 expression in white fat and UCP1 expression in brown fat and that resistance to obesity is correlated with this early, selective induction of UCP1 and UCP2 and is not associated with changes in expression of UCP3.