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Elevated serum resistin is implicated in insulin resistance associated with obesity and type 2 diabetes mellitus. Alcohol consumption interferes with the nutritional status, metabolic and hormonal activity of the drinker. Impact of ethanol intake on resistin level and resistin metabolic effects is unknown. Effect of long-time (28 days) ad libitum moderate alcohol (6% ethanol solution) intake on serum resistin and resistin mRNA level in adipose tissue of rats (A) was compared to control (C) and pair-fed (PF) animals. PF rats were fed the same caloric amount as A rats on previous day. Alcohol consumption resulted in reduction of food and energy intake, decreased body mass gain, epididymal fat pads mass and smaller adipocytes (vs. C rats). Alcohol intake significantly increased serum resistin and glucose, insulinemia remained unchanged. Systemic insulin resistance was not proved by HOMA, QUICKI and McAuley indexes, but impaired insulin effect on glucose transport in isolated adipocytes was present. Elevated serum resistin was positively correlated with glycemia (r = 0.88, p < 0.01) and negatively with fat cell size (r = -0.73, p < 0.05). High resistin level as the consequence of long-time alcohol intake could contribute to smaller adipocytes, higher glycemia, attenuation of insulin-stimulated glucose transport in adipocytes. Diminished resistin gene expression in adipose tissue of A and PF rats was present.

In order to better understand the mechanisms leading to insulin resistance, the number of fat tissue insulin receptors, their affinity and insulin receptor protein in rats with monosodium glutamate-induced obesity were studied. Obese rats displayed significantly lower number of insulin receptors with high affinity. Surprisingly, the amount of insulin receptor protein was significantly elevated in these animals. The same relations have been already reported for angiotensin II binding and AT1 receptor protein in the same model of obesity. Therefore we suggest an existence of general defect of adipocyte cell membrane in monosodium glutamate-induced obesity characterized by the presence of high quantity of impaired receptor protein.

Age-related hypertrophy of adipose tissue has been associated with a significant decrease in the number of angiotensin II receptors. The aim of this study was to investigate the characteristics of angiotensin II receptors in hypertrophic adipose tissue in animal obesity model using rats postnatally treated with monosodium glutamate. Angiotensin II is known to induce hypertrophy in several tissues of the cardiovascular system and might do the same in fat tissue. The expression and binding properties of angiotensin II AT(1) receptors in epididymal fat tissue of adult rats were studied using membrane-binding, RT-PCR, and immunoblotting. The amount of AT(1) receptor mRNA did not differ significantly between obese and control rats. Despite that glutamate-treated rats displayed approximately 4-times more AT(1) receptor immunoreactive protein content in fat tissue cell membranes than the controls did. In contrast, binding experiments showed a significant (40.3 +/- 6.2 %) decrease of (125)I-Sar(1)-Ile(8)-angiotensin II-binding to fat tissue cell membranes in obese rats compared to controls. In conclusion, the present study provides evidence for the low binding properties associated with an accumulation of AT(1) receptor protein in cell membranes of the fat tissue of rats with glutamate-induced obesity. Discrepancies among angiotensin II-binding, AT(1) receptor protein, and AT(1) receptor mRNA levels indicate a possible defect in the receptor protein, which remains to be identified. The results obtained support a role of angiotensin II and AT(1) receptors in the pathogenesis of obesity.

Angiotensin II exerts its action via at least two distinct receptor subtypes designated AT1 and AT2. AT1 receptors seem to be responsible for most of the known angiotensin II effects while the role of AT2 receptors is not yet clear. Adipocytes of adult rats express exclusively the AT1 subtype. Angiotensin II stimulates prostacyclin release in adult rat adipocytes and in mouse preadipocytes. In the latter prostacyclin release is completely blocked by an AT2 receptor antagonist. Adipocyte angiotensin II receptors seem to be regulated by age and fat mass. Blockade of these receptors by an AT1 antagonist seems to prevent adipose tissue hypertrophy. Moreover, adipose tissue contains all the main components of the renin-angiotensin system such as angiotensinogen, angiotensin converting enzyme, angiotensin II and angiotensin II receptors. Angiotensinogen expression in adipocytes is stimulated by a high fat diet concurrent with enlargement of fat mass, associated with insulin resistance. Angiotensin converting enzyme inhibitors improve insulin sensitivity. Taken together, there is evidence of interaction between insulin and angiotensin II in regulation of adipose tissue metabolism and cellularity. Clarification of these interactions could lead to significant progress in pharmacological treatment of obesity and its comorbidity.

High sucrose diet-induced insulin resistance and mild glucose intolerance are associated with decreased insulin binding to isolated adipocytes and reduced insulin action in adipose tissue. Enhanced dietary intake of omega-3 polyunsaturated fatty acids (n-3-FA) counteracts these disorders. To provide more information on the possible role of membrane-related glucose transport processes, basal and insulin-stimulated 2-deoxy-D-3H glucose uptake was evaluated in isolated adipocytes obtained from rats on various dietary regimens. For 2 weeks animals were fed three different isocaloric (18 cal% proteins, 19 cal% fat, and 63 cal% carbohydrate) diets: (1) a standard rat chow (B), (2) a high sucrose diet (S, 63 cal% sucrose), or (3) an S diet supplemented with marine fish oil (S + FO, Martens, 30 wt% of n-3-FA). High dietary n-3-FA intake resulted in a significant decline in both basal (0.05 +/- 0.01 pmol/10(6) fat cells; mean +/- SEM) and insulin-stimulated (10(-6) M) (0.20 +/- 0.01) glucose uptake when compared with the control (basal: 0.12 +/- 0.02; insulin: 0.35 +/- 0.02) and/or the S group (basal: 0.18 +/- 0.03; insulin: 0.43 +/- 0.03), indicating decreases in insulin responsiveness and sensitivity (ED50: B: 0.03 +/- 0.01; S: 0.03 +/- 0.01; S + FO: 0.73 +/- 0.2 nM; p < 0.01 for S + FO vs B and S + FO vs S). Fish oil supplementation induced an increase in adipocyte size (B: 69 +/- 1.6; S: 70 +/- 2.5 and S + FO: 76 +/- 2.2 microns; B: S + FO p < 0.05) and a decrease in plasma membrane microviscosity (B: 4.08 +/- 0.3; S: 5.39 +/- 0.5; S + FO: 3.10 +/- 0.3; p < 0.05). Rates of basal and insulin-stimulated glucose uptake did not correlate with plasma membrane microviscosity; however, a negative relation to fat cell size was found (r = -0.484; p < 0.05). On the other hand, a positive correlation between both basal (r = 0.504; p < 0.05) and insulin-stimulated (10(-6) M, r = 0.640; p < 0.02) glucose uptake and blood glucose levels was observed. In conclusion, these data (a) suggest a less important role of diet-induced changes in plasma membrane microviscosity for glucose uptake in adipose tissue, and (b) leave unclear the mechanism of why dietary fish oil decreases the sensitivity of glucose uptake to insulin in isolated rat adipocytes.

The role of corticosterone in the changes of insulin receptors of rat adipocytes during hypokinesia was investigated. Three groups of adult male Wistar rats (1. intact; 2. adrenalectomized; 3. dexamethasone treated) were exposed to hypokinesia for various period. The plasma levels of corticosterone, insulin and glucose and the binding of insulin (125I-TyrA-14 monoiodoinsulin) to isolated adipocytes were determined. A significant increase of plasma corticosterone level and a decrease of insulin binding to adipocytes were found in rats exposed to hypokinesia for one day. After 3 and 5 days of hypokinesia the corticosterone level in plasma was decreased to the concentration observed in the control animals. Also the binding of insulin to adipocytes returned to the values found in control group. In adrenalectomized rats exposed to hypokinesia no changes of insulin receptors in adipocytes were noted. The treatment of rats with dexamethasone (both, the intact and adrenalectomize ones) resulted in a decrease of insulin binding in fat cells. These results showed that an increase of corticosterone in plasma after the short term exposure to hypokinesia or the injection of dexamethasone to intact or adrenalectomized animals are followed by the decrease of insulin receptors in adipocytes suggesting that glucocorticoids participate in the regulation of insulin receptors in adipocytes during short term hypokinesia.

The increase of nonesterified fatty acid (NEFA) concentration in plasma was observed in rats subjected to hypokinesia for 1-60 days. In the period of recovery (7 and 21 days after 60 days immobilization) the content of NEFA returned to control values. The increase of fatty acid release from adipose tissue was observed in hypokinetic rats, however the stimulation of lipolysis by norepinephrine was lower in rats exposed to hypokinesis. The decrease of the binding capacity and a diminished number of beta-adrenergic receptors were found in animals after hypokinesia. The augmentation of the incorporation of glucose into lipids and the marked increase in the stimulation of lipogenesis by insulin were found in adipose tissue of rats subjected to long-term hypokinesia. These results showed an important effect of hypokinesia on lipid mobilization, on lipogenesis and on the processes of hormone regulation in adipose tissue.

The authors described the effect of premature weaning on the fatty acid spectrum in the retroperintoneal fat of female rats during ontogenesis. Premature weaning reduced the lower fatty acid content [decanoic acid C 10:0, lauric acid C 12:0, myristic acid C 14:0] in 30- to 90-day-old rats, but in further development no differences between the amount of these fatty acids were observed in suckled and prematurely weaned animals. These changes concurred with the fatty acid composition of the relevant diet (rat milk and a standard laboratory diet). Changes induced in the amount of other acids by premature weaning were not permanent in character, with the exception of stearic acid C 18:0 and linoleic acid C 18:3, which were raised at 720 days in the retroperitoneal fat of prematurely weaned rats. The amount of lower saturated fatty acids fell with advancing age, whereas oleic C 18:1, linolic C 18:2 and linolenic C 18:3 acid rose.

The activity of the enzymes involved in aminoacid metabolism (tyrosine aminotransferase, TAT, tryptophan pyrrolase TP, serine dehydratase, SD) with rapid response to glucocorticoids and enzymes requiring for activity increase repeated administration of corticosterone (alanine aminotransferase, ALT, aspartate aminotransferase, AST) in liver, the changes of lipolysis in adipose tissue and the plasma corticosterone levels were studied in rats subjected to space flight (F), in animals from synchron model experiments (SM, simulated conditions of space flight in laboratory) and in intact controls (C). The increase of plasma corticosterone concentration and of the activity of rapidly (TAT, TP, SD) and slowly activating enzymes (ALT, AST) was found in F group 6-10 hr after space flight (18.5 days on biosatellite COSMOS 1129). This suggested the presence of acute-stress (associated primarily with the landing) and chronic stress induced hypercorticosteronemia during the flight. After the short 6-day period of recovery the plasma corticosterone concentrations and the activities of liver enzymes returned to control levels. The exposition of animals to repeated immobilization stress showed higher response of corticosterone levels in flight rats as compared to intact controls. No changes in basal lipolysis were observed in flight rats in comparison to intact controls, however the stimulation of lipolysis by norepinephrine was lower in animals from F and SM groups. This lower response of lipolytic processes to norepinephrine was found in flight animals also after six days period of recovery. These results showed that there are important changes in the regulation of lipolytic processes in adipose tissue of rats after space flight and in the conditions of model experiments.

The influence of different neonatal nutrition on the properties of insulin receptor in isolated adipocytes was studied. The changes of neonatal nutrition were achieved by adjustment of the number of sucklings to 4, 8 and 14 per one litter. After weaning (at the age of 30 days) the animals were fed standard pelleted diet ad libitum. The isolated fat cells from male rats neonatally overfed (i.e. 4 per litter), underfed (i.e. 14 per litter) and control group (i.e. 8 per litter) aged 30, 60, 120 and 500 days were prepared and used for insulin binding studies. The results showed that the total number of insulin receptors is the same in small and large adipocytes from neonatally over- or underfed animals, but a negative correlation between insulin binding sites per unit of surface area and fat cell size was found. The smaller adipocytes from neonatally underfed rats apparently showed a higher binding affinity to insulin as compared to larger fat cells from neonatally overfed animals.

Differences in the response of isolated adipocytes to insulin were found in relation to the age and early postnatal nutrition. In old rats (15 months) an impaired stimulation of 14C-glucose incorporation into lipids was found after insulin as compared to young animals (1 or 2 months old). In isolated fat cells from young neonatally underfed rats a higher increase of insulin induced lipogenesis was observed than in controls. The response to insulin, however, was not influenced by neonatal nutrition inold rats. Glucose oxidation in the diaphragm was also lower in older animals (4 months) than in young (1 month) rats. The stimulation of glucose oxidation by insulin was higher in neonatally underfed rats as compared to overfed ones during the suckling period. The rise of glucose oxidation after insulin decreased with age. These results showed that the response of muscular and adipose tissue decreases by age and that nutrition during the early postnatal period may affect the influence of insulin on the metabolsim of glucose in adipose and muscular tissue in young animals.

The content of cAMP, the release of glycerol and nonesterified fatty acids (NEFA) of adipose tissue with and without the stimulation by ACTH and norepinephrine were determined in young and old rats. After the lipid mobilizing hormones lowered concentration of cAMP and impaired stimulation of lipolytic activity were found in old rats. Furthermore, less stimulation of glycerol and NEFA release by cAMP was observed in these animals. These results suggested that in old animals a lower lipolytic activity per tissue and lipid mass is available in intact and hormone stimulated fat tissue and therefore the accumulation of lipids in fat depots is facilitated.

The rats flown aboard Cosmos-782 showed a significant increase in the activity of tyrosine aminotransferase and tryptophan pyrolase, i. e. the enzymes whose activity depends on the corticosterone level. The synchronous rats displayed a small increase in the enzyme activity. The flight and synchronous animals exhibited a slight increase in the activity of gluconeogenetic enzymes and a decrease in the activity of glucose-6-phosphatase. Immediately after flight and, to a lesser extent, after the synchronous experiment the activity of lipogenetic enzymes decreased. On the R+25 day the enzyme activity remained unchanged. The study of lipogenesis in the epididymal fat, using C14-glucose incorporation into lipids, did not reveal any differences in the flight and synchronous rats. The findings demonstrated that changes in the enzyme activity induced by the flight and synchronous experiments returned to the normal during readaptation.