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PubMed1998

Adipose tissue ob mRNA expression in humans: discordance with plasma leptin and relationship with adipose TNFalpha expression.

Elevated plasma leptin levels are found in obese humans, suggesting a defect in the function of leptin in regulating body weight and adiposity. In 53 subjects covering a broad range of adiposity, we examined the relationships between plasma leptin, adipose tissue ob mRNA levels, and adipose tissue TNF mRNA. There was a highly significant correlation between plasma leptin levels and every index of adiposity. In contrast, the relationship between ob mRNA levels and adiposity was weak. Adipose tissue from obese subjects demonstrated higher ob mRNA levels than adipose tissue from lean subjects (lean: 0.49+/-0.05; obese 0.87+/-0.09 arbitrary units, P< 0.05). However, there was no significant correlation between body fat and ob mRNA level. In addition, there was no significant relationship between ob mRNA levels and plasma leptin levels, which were measured in the same subjects. In addition to the measure of ob mRNA levels, adipose TNF mRNA levels were measured in 18 subjects. TNF mRNA levels varied with ob mRNA levels (r = 0.44, P = 0.06). These data show that plasma leptin levels are not directly related to adipose tissue ob mRNA levels, suggesting posttranscriptional regulation of leptin expression, either at the level of the adipocyte, or by alteration of plasma leptin degradation or clearance. In addition, the parallel changes in ob and TNF mRNA in adipose tissue suggest that these two important factors in the defense against obesity may be regulated similarly.

Adipose Tissue↗
PubMed1989

Ontogenetical changes in adipose tissue of the cat: convertible adipose tissue.

The ultrastructural characteristics of the inguinal, interscapular, and perirenal adipose tissue in kittens and cats were studied. There were no qualitative differences among adipocytes in the three anatomical areas. The only recorded difference was in the amount of lipids stored in the adipocytes in younger stages. Immediately after birth lipids occupied 25% of the volume in the inguinal area, 15% in interscapular fat tissue, and 10% in perirenal fat tissue. At this stage the adipose tissue morphologically resembled brown adipose tissue (BAT) of rodents. Two weeks after birth, lipids accumulated and adipocytes in the inguinal area became unilocular and appeared similar to white adipose tissue (WAT). A similar transition occurred approx 25 days after birth in interscapular fat and approx 6 weeks after birth in the perirenal area. No morphological signs of any cell degradation or destruction, nor any increased activity of preadipocytes, were seen during this conversion from BAT-like to WAT-like adipose tissue. The conversion of the adipose tissue was correlated with a decrease in vascularization and innervation, a loss of intercellular connections, and a changed mitochondrial population. Mitochondria in multilocular adipocytes resembled those in typical BAT which contain uncoupling protein ("UC-mitochondria"). After conversion to unilocular adipocytes the amount of mitochondria was halved, their cristae even more reduced, and their appearance was of a WAT-type (UCP-lacking mitochondria, which are coupled under physiological conditions; "C-mitochondria"). Since this category of adipose tissue differs from both typical brown and white adipose tissue, the name "convertible adipose tissue" (CAT) is proposed. Apparently adipose tissue from comparatively large mammals is of this convertible type.

Adipose Tissue↗
PubMed2000

Hyperleptinemia is more closely associated with adipose cell hypertrophy than with adipose tissue hyperplasia.

OBJECTIVES: To investigate the relationships of fat cell weight (FCW) as well as of estimated total adipose cell number to fasting plasma leptin concentration. DESIGN: Cross-sectional correlational study. SUBJECTS: A sample of 63 men (mean age+/-s.d.: 36+/-4 y) and 42 premenopausal women (35+/-5 y). MEASUREMENTS: Adipose tissue (AT) biopsies were obtained in order to determine FCW as well as estimated adipose cell number. Fasting plasma leptin and insulin concentrations as well as various fatness and body fat distribution variables (underwater weighing and computed tomography) were also measured. RESULTS: In both genders, mean FCW as well as the estimated adipose cell number were significantly correlated with body fatness and AT distribution variables (0.41</=r</=0.84). Larger abdominal (P<0.005) and femoral (P<0.0001) FCW were found in women than in men. This gender difference in adipose cell size was associated with increased leptin concentrations in women compared with men. In both genders, increased abdominal FCW was associated with higher plasma leptin concentrations (men: r=0.38, P<0.005 and women: r=0.55, P<0.0001). However, the association between femoral FCW and leptinemia was only significant in women (r=0.45, P<0.005). Contrary to women, plasma leptin concentrations were associated with estimated adipose cell number in men (r=0.59, P<0.0001). Multiple regression analyses revealed that gender (43.3%), mean FCW (16.2%) and the estimated adipose cell number (10.1%) were significant predictors of fasting leptinemia. CONCLUSIONS: Results of the present study indicate that in men and women, adipose cell hypertrophy is associated with increased plasma leptin concentrations. This finding provides further support to the observation that adipose tissue leptin secretion may be regulated, at least to a certain extent, by adipocyte size. Thus, the present study suggests that the higher plasma leptin concentrations found in women than in men could be partly explained by the well documented gender difference in adipose cell size and number.

Adipocytes↗
PubMed2001

Adipose angiotensinogen is involved in adipose tissue growth and blood pressure regulation.

White adipose tissue and liver are important angiotensinogen (AGT) production sites. Until now, plasma AGT was considered to be a reflection of hepatic production. Because plasma AGT concentration has been reported to correlate with blood pressure, and to be associated with body mass index, we investigated whether adipose AGT is released locally and into the blood stream. For this purpose, we have generated transgenic mice either in which adipose AGT is overexpressed or in which AGT expression is restricted to adipose tissue. This was achieved by the use of the aP2 adipocyte-specific promoter driving the expression of rat agt cDNA in both wild-type and hypotensive AGT-deficient mice. Our results show that in both genotypes, targeted expression of AGT in adipose tissue increases fat mass. Mice whose AGT expression is restricted to adipose tissue have AGT circulating in the blood stream, are normotensive, and exhibit restored renal function compared with AGT-deficient mice. Moreover, mice that overexpress adipose AGT have increased levels of circulating AGT, compared with wild-type mice, and are hypertensive. These animal models demonstrate that AGT produced by adipose tissue plays a role in both local adipose tissue development and in the endocrine system, which supports a role of adipose AGT in hypertensive obese patients.

Adipocytes↗
PubMed2000

Alterations in fetal adipose tissue leptin expression correlate with the development of adipose tissue.

Control pig fetuses and fetuses hypophysectomized (hypox) at 70 days of gestation were treated with hormones on day 90. At 105 days of gestation, subcutaneous adipose tissue was prepared for morphological studies, leptin Northern blot and Western blot analysis. Fetal ontogeny studies showed that leptin mRNA in adipose tissue increased with morphological development, and the highest level of leptin mRNA was observed in 105-day fetal pigs. In hypox fetuses, levels of leptin mRNA were similar to those in controls. Treatment with either hydrocortisone (HC) or thyroxine (T(4)) resulted in a slight increase in leptin mRNA levels in hypox fetuses but not in intact fetuses. Supplementation with both HC and T(4) markedly stimulated leptin mRNA expression in both hypox and intact fetuses. Morphological data showed that hypox slightly enhanced lipid accretion and treatment of hypox fetuses with HC and T(4) increased lipid accretion to a greater degree than did either HC or T(4) alone. However, serum leptin levels were not influenced by age, hypox or hormone treatment. Leptin protein expression was not detected in adipose tissue of hypox or intact fetuses regardless of hormone treatment. Leptin protein was detected in adipose tissue of 7-day-old pigs and placenta. As compared to 7-day postnatal adipose tissue, placenta showed a higher level of leptin protein expression. Leptin mRNA expression in fetal adipose tissue was not correlated with body weight and organ weight. The expression of long-form leptin receptor mRNA was detected in fetal adipose tissue. Our results indicate that adipose tissue leptin may not be the main source of serum leptin in the fetus and may not be involved in general prenatal growth and development. But adipose tissue leptin may act as an autocrine or paracrine factor in the development of fetal adipose tissue.

Adipose Tissue↗
PubMed2003

The lipolytic responsiveness to endotoxin in subcutaneous adipose tissue is greater than mesenteric adipose tissue.

In sepsis and endotoxemia, metabolism is characterized by accelerated catabolism. In the present study, lipolytic responsiveness of subcutaneous and mesenteric adipose tissue to the sub-lethal dose of endotoxin injection (5 mg/kg) was evaluated using microdialysis techniques in rats. All rats were urethane-anesthetized and implanted with microdialysis probes in their subcutaneous and mesenteric adipose tissue. Lipolysis in each adipose tissue was assessed by measuring the glycerol concentration (an index of lipolysis) in the dialysate from the microdialysis probe. Lipolysis was continuously monitored for 7-hours, prior to and following the injection of endotoxin. The control animals were injected with only saline. Lipolysis in subcutaneous adipose tissue began to increase by 1-hours after endotoxin injection, and reached a peak 60% higher than the basal level by 2-hours after injection. This activated lipolysis after endotoxin was markedly greater than that in the control animals and maintained for 5 hours. In mesenteric adipose tissue, lipolysis after endotoxin injection was greater than in the control animals, but not significant. The endotoxin-induced lipolysis in the subcutaneous adipose tissue was significantly greater than that in the mesenteric adipose tissue. We conclude that the sub-lethal dose of endotoxin injection cause active lipolysis in adipose tissues, and that the lipolytic responsiveness to endotoxin in subcutaneous adipose tissue is greater than in mesenteric adipose tissue.

Adipose Tissue↗
PubMed2006

Mesenteric adipose tissue-derived monocyte chemoattractant protein-1 plays a crucial role in adipose tissue macrophage migration and activation in obese mice.

OBJECTIVE: To determine whether chemokines, which play a pivotal role in monocyte/macrophage trafficking, modulate macrophage infiltration into and activation in the adipose tissues. RESEARCH METHODS AND PROCEDURES: Various types of adipose tissue were isolated from different fat depots (e.g., mesenteric, epididymal, renal, and subcutaneous adipose tissues) from obese mice fed a high-fat diet and from non-obese controls fed a standard diet. The isolated tissues were cultured for 24, 48, and 72 hours. The level of monocyte chemoattractant protein-1 (MCP-1) expression and the amount of protein released were measured by reverse transcriptase-polymerase chain reaction or enzyme-linked immunosorbent assay, respectively. Chemotaxis assay was performed to measure the degree of macrophage migration. Macrophage activation was estimated by measuring the concentrations of nitric oxide and tumor necrosis factor alpha. RESULTS: The level of MCP-1 mRNA expression, protein content, and the amount of protein released significantly increased in the adipose tissues from the obese mice compared with those from the non-obese mice. The mesenteric adipose tissue produced the highest levels of MCP-1 protein among the four different fat depots. Mesenteric adipose tissue-conditioned medium induced the highest degree of macrophage migration and strongly induced macrophages to produce proinflammatory mediators such as nitric oxide and tumor necrosis factor alpha. The neutralization of MCP-1 in the adipose tissue-conditioned medium significantly inhibited the migration and activation of macrophages. DISCUSSION: Our findings suggest that MCP-1 plays a crucial role in adipose tissue inflammatory response by activating and inducing the infiltration of macrophages into adipose tissues. MCP-1 may be closely associated with visceral obesity-related complications and, thus, may be a useful therapeutic target for modulating visceral obesity-related diseases.

Adipose Tissue↗
PubMed2002

Adiposity, adipose tissue distribution and mortality rates in the Canada Fitness Survey follow-up study.

OBJECTIVE: To compare mortality rates across indicators of adiposity and relative adipose tissue distribution in the Canadian population. SUBJECTS: The sample included 10,323 adult participants 20-69 y of age from the Canada Fitness Survey who were monitored for all-cause mortality over 13 y. METHODS: BMI, waist circumference (WC) and the sum of five skinfolds (SF5) were indicators of adiposity, and the first principal component of skinfold residuals (PC1) represented subcutaneous adipose tissue distribution. Proportional hazards regression was used to estimate relative mortality risk from mortality rates across levels of adiposity and adipose tissue distribution, controlling for the confounding effects of age, smoking status and alcohol consumption. RESULTS: :Significant curvilinear (J-shaped) relationships in men and linear relationships in women were observed between BMI, WC and SF5 and all-cause mortality rates. PC1 was not related to mortality rates in either men or women. In women, the inclusion of the other indicators of adiposity and adipose tissue distribution did not significantly add to the prediction of mortality rates beyond BMI; however, combinations of BMI and both WC and SF5 produced significant models in men. CONCLUSION: The results support the hypothesis that overall level of adiposity is an important predictor of all-cause mortality, more so than the relative distribution of subcutaneous body fat, once overall level of body fatness has been accounted for.

Adipose Tissue↗
PubMed1982

Relationships among growth, adipose cell size, and lipid metabolism in ruminant adipose tissue.

In early postnatal development, growth of adipose tissue is due to both cellular hypertrophy and hyperplasia. Adipose cell (adipocyte) hypertrophy is the major mechanism in fattening of ruminants grown to market weight, although evidence is accumulating that preadipose cells can proliferate postnatally, even in mature animals. In interfasicular adipose tissue (marbling), however, small adipose cells are present and their number makes a positive contribution to the size of this fat depot in ruminants of market weight. Present information does not indicate whether these small cells are newly synthesized cells or are cells that differentiated early in postnatal development and fill with lipid at some later time. Limitations on detecting small adipose cells in cell-counting techniques are partly responsible for conflicting conclusions on the cellular basis for adiposity. Nutritional modification of adipose cell number has been reported in rodents. However, the extreme nutritional modifications required to alter cell number have little practical application in the growth of ruminants for meat production. Adipose cells of various sizes respond differently in the esterification and synthesis of fatty acids. The greater rates of lipid synthesis from acetate in large adipose cells may be related to increased uptake of substrate in cells with a large surface area.

Acetates↗
PubMed1996

Does visceral adipose tissue differ from subcutaneous adipose tissue in fatty acid content?

OBJECTIVE: To determine whether intra-abdominal adipose tissue differs from subcutaneous adipose tissue in fatty acid content. DESIGN: Cross-sectional study of patients undergoing exploratory laparotomy, with adipose tissue sampling from subcutaneous, omental, mesenteric and retroperitoneal sites. SUBJECTS: Nineteen subjects, 8 men and 11 women, with a mean age of 64 (range 39-80), mean weight 78.9 kg (range 51-157) and mean body mass index of 27.5 (range 19.2-51.4). Fourteen of the 19 were undergoing surgery for colorectal cancer. MEASUREMENTS: Fatty acid content was assessed by gas chromatography and was compared between sites and between patients using general linear modeling. Spearman correlation coefficients were used to assess the association between subcutaneous and visceral adipose tissue. RESULTS: For each of 17 fatty acids analyzed, there was a statistically significant difference in mean fatty acid values across individuals (p < 0.001). For seven of the fatty acids, there was a borderline or significant difference in mean fatty acid values across site, but there was no consistent pattern for one site differing from the others. Subcutaneous adipose tissue fatty acid content was highly correlated to visceral adipose tissue for saturated, unsaturated and trans fatty acids (p < 0.05 for 13 of 17 fatty acids). Variability across individuals was much greater than across site. The total explained variability (R2) for each fatty acid ranged between 49 and 93%, with the vast majority contributed by differences between individuals. CONCLUSION. Fatty acid content of subcutaneous abdominal adipose tissue is a good approximation of visceral adipose tissue. Because variability in fatty acid content is much larger between individuals than within a single individual across sites, subcutaneous abdominal adipose tissue fatty acid content can be used as a distinguishing characteristic among human populations.

Adipose Tissue↗
PubMed1983

High-energy diets produce different effects on fatty acid synthesis in brown adipose tissue, white adipose tissue and liver in the rat.

The influence of feeding rats a high-energy diet for 7 days on fatty acid synthesis in brown adipose tissue, white adipose tissue and liver of the rat was investigated. The incorporation of 3H2O and [U-14C]glucose into fatty acid was measured in vivo. The rats fed the high-energy diets had higher rates of fatty acid synthesis in white adipose tissue than the controls fed on chow, while fatty acid synthesis in brown adipose tissue and liver was either decreased or unchanged relative to that of controls fed on chow. After an oral load of [U-14C]glucose the incorporation of radioactivity into tissue fatty acid was several-fold higher in brown adipose tissue than in white adipose tissue in rats fed on chow. In rats fed the high-energy diets, incorporation of radioactivity into fatty acid in brown adipose tissue was decreased while that into white adipose tissue was either increased (Wistar rats) or unchanged (Lister rats).

Adipose Tissue↗
PubMedDate not supplied

The effect of intermittent cold treatment on the adipose tissue of the cat. Apparent transformation from white to brown adipose tissue.

Young cats (Felis domestica), aged 10-13 weeks, were intermittently exposed to a temperature of -30 degrees C for two periods of 1 hr per day. Animals were sacrificed on the 7th day and adipose tissue from the perirenal, pericardial, axillary, interscapular, and subcutaneous-inguinal depots was examined by electron microscopy and analysed stereologically. All examined depots were morphologically changed after cold treatment. Adipose tissue of perirenal, pericardial, and axillary depots showed a greater decrease in lipid content than the interscapular and subcutaneous-inguinal depots, but other changes were similar. Compared to the control group, which consisted of typical white adipose tissue, the diameter of adipose cells examined after cold treatment was diminished, in extreme cases to 18 micron (from 75 micron in the control group). The number of capillaries per cell was doubled (as evaluated on semithin sections). The most dramatic changes were observed in the mitochondria. Their volume increased to 0.48 micron 3 (from 0.13 micron 3 in the control), and the surface density of mitochondrial cristae per mitochondrial volume increased to 50 micron 2/micron 3 (from 32 in the control). Pleomorphism in mitochondrial size and inner structure and the presence of intramitochondrial electron-dense bodies and crystalline structures led us to conclude that the cold stress induced an increase in the absolute number of mitochondria in the adipose cells. The adipose tissue after cold treatment thus morphologically resembled the brown adipose tissue of cold-acclimated rodents. This implies that the adipose tissue of young cats can change its morphology and function, depending on the requirements of the organism.

Acclimatization↗
PubMed2000

Dietary n-3 fatty acids affect mRNA level of brown adipose tissue uncoupling protein 1, and white adipose tissue leptin and glucose transporter 4 in the rat.

We examined the effect of dietary fats rich in n-3 polyunsaturated fatty acids (PUFA) on mRNA levels in white and brown adipose tissues in rats. Four groups of rats were fed on a low-fat diet (20 g safflower oil/kg) or a high-fat diet (200 g/kg) containing safflower oil, which is rich in n-6 PUFA (linoleic acid), or perilla (alpha-linolenic acid) or fish oil (eicosapentaenoic and docosahexaenoic acids), both of which are rich in n-3 PUFA, for 21 d. Energy intake was higher in rats fed on a high-safflower-oil diet than in those fed on low-fat or high-fish-oil diet, but no other significant differences were detected among the groups. Perirenal white adipose tissue weight was higher and epididymal white adipose tissue weight tended to be higher in rats fed on a high-safflower-oil diet than in those fed on a low-fat diet. However, high-fat diets rich in n-3 PUFA, compared to a low-fat diet, did not increase the white adipose tissue mass. High-fat diets relative to a low-fat diet increased brown adipose tissue uncoupling protein 1 mRNA level. The increases were greater with fats rich in n-3 PUFA than with n-6 PUFA. A high-safflower-oil diet, compared to a low-fat diet, doubled the leptin mRNA level in white adipose tissue. However, high-fat diets rich in n-3 PUFA failed to increase it. Compared to a low-fat diet, high-fat diets down-regulated the glucose transporter 4 mRNA level in white adipose tissue. However, the decreases were attenuated with high-fat diets rich in n-3 PUFA. It is suggested that the alterations in gene expression in adipose tissue contribute to the physiological activities of n-3 PUFA in preventing body fat accumulation and in regulating glucose metabolism in rats.

Adipose Tissue↗
PubMed2004

Isomers of conjugated linoleic acid decrease plasma lipids and stimulate adipose tissue lipogenesis without changing adipose weight in post-prandial adult sedentary or trained Wistar rat.

The respective effects and interactions of supplementation with two conjugated linoleic acid (CLA) isomers and exercise on plasma metabolic profile, activity of lipogenic enzymes and cellularity in two adipose tissue sites, those of the liver and heart, were examined in adult Wistar rats. Rats that were either sedentary or exercise-trained by treadmill running were fed one of four diets: a diet without CLA; a diet with either 1% cis 9, trans 11 CLA or 1% trans 10, cis 12 CLA; or a mixture of both isomers (1% of each) for 6 weeks. We observed that the exercise decreased lipogenic enzyme activities in epididymal and perirenal adipose tissue. Plasma cholesterol, insulin, and leptin concentrations were lower in exercise-trained rats than in sedentary rats. The ingestion of either CLA mixture or the trans 10, cis 12 CLA increased lipogenic enzyme activities in epididymal tissue and more markedly in perirenal adipose tissue, especially in sedentary rats, and without affecting adipose tissue weight or cellularity. A similar effect of trans 10, cis 12 CLA was observed in regard to malic enzyme activity in the liver. In addition, this isomer decreased plasma lipid and urea concentrations and increased plasma 3-hydroxybutyrate levels. The ingestion of cis 9, trans 11 CLA increased fatty acid synthase activity in perirenal adipose tissue in sedentary rats and decreased plasma cholesterol and leptin concentrations. These results show that isomers of CLA decrease plasma lipids and stimulate adipose tissue lipogenesis without changing adipose weight in adult sedentary or exercise-trained rat, thus suggesting a stimulation of adipose tissue turnover.

Adipose Tissue↗
PubMed2006

Regulation of secreted protein acidic and rich in cysteine during adipose conversion and adipose tissue hyperplasia.

OBJECTIVE: To explore the regulation of secreted protein acidic and rich in cysteine (SPARC) expression and its role in adipose tissue. RESEARCH METHODS AND PROCEDURES: We studied the regulation of SPARC expression in transgenic mice expressing the human beta3 and alpha2 adrenergic receptors on a murine beta3 adrenergic receptor null background that became obese under a high-fat diet mainly as a result of adipose tissue hyperplasia. Furthermore, we analyzed its expression in human adipose tissue and its regulation during adipocyte differentiation. RESULTS: SPARC protein in adipose tissue was increased in obese transgenic mice compared with control mice, indicating that SPARC expression was associated with adipose tissue hyperplasia. Both SPARC mRNA and protein were detected in human adipose tissue. Comparing adipocytes and vascular stroma, we found that SPARC expression was mainly associated with the adipocyte fraction. Consistent with this, SPARC transcript increased during differentiation of human primary preadipocytes. 3T3-L1 preadipocytes showed an increase in SPARC expression in differentiated cells but with biphasic expression during the process. After induction in committed cells, SPARC mRNA and protein levels declined as differentiation began and returned to elevated levels in fully differentiated adipocytes. DISCUSSION: SPARC expression correlated with adipose tissue hyperplasia and adipogenesis. Therefore, SPARC seems to play a role in adipose tissue physiology as it is involved in growth and differentiation.

Adipocytes↗