Biomedical subjects

B Richelsen

Publications and source records attributed to B Richelsen.

At least 37 records · Page 2Linked to original sources

PubMed2001

The obese Göttingen minipig as a model of the metabolic syndrome: dietary effects on obesity, insulin sensitivity, and growth hormone profile.

The objective of the study reported here was to induce obesity in the female Göttingen minipig to establish a model of the human metabolic syndrome. Nine- to ten-month-old female Göttingen minipigs received a high-fat high-energy (HFE) diet or a low-fat, low-energy (LFE) diet. The energy contents derived from fat were 55 and 13 %, respectively. After 5 weeks, animals were subjected to dual energy x-ray absorptiometry (DEXA) scanning, intravenous glucose tolerance testing (IVGTT), and 6-h growth hormone profile recording. After treatment, mean body weight of pigs of the LFE group was 21.0 +/- 0.4 kg, and was 26.8 +/- 0.2 kg in pigs of the HFE group (P < 0.0001). The DEXA scanning indicated that the fat content of the LFE group was 10.0 +/- 1.2 % versus 15.2 +/- 0.7 % in the HFE group (P < 0.003). Triglycerides concentration was significantly (P < 0.05) increased in pigs of the HFE group (0.24 +/- 0.03 mM), compared with that in pigs of the LFE group (0.13 +/- 0.04 mM). Preprandial plasma glucose and insulin concentrations were not affected, but insulin area under the curve during IVGTT was significantly high in the obese animals. Growth hormone (GH) secretion was low in both groups of pigs. The obese minipig shares some of the metabolic impairments seen in obese humans, and may thus serve as a model of the metabolic syndrome.

Absorptiometry, Photon↗

PubMed2000

Systemic administration of epidermal growth factor increases UCP3 mRNA levels in skeletal muscle and adipose tissue in rats.

We have previously reported that systemic epidermal growth factor (EGF) treatment in rats reduces the amount of adipose tissue despite an unaltered food intake. The mitochondrial uncoupling proteins (UCP2 and UCP3) are thought to uncouple the respiratory chain and thus to increase energy expenditure. In order to find out whether the UCP system was involved in the EGF-induced weight loss, the effects of EGF on UCP2 and UCP3 in adipose tissue and skeletal muscle were investigated in the present study. Eight rats were treated with placebo or EGF (150 microg/kg/day) for seven days via mini-osmotic pumps. The EGF-treated rats gained significantly less body weight during the study period than the placebo-treated animals and had significantly less adipose tissue despite a similar food intake. The placebo group and the EGF group had similar UCP2 mRNA expression (in both adipose tissue and skeletal muscle), whereas the EGF-treated group compared to the placebo group had significantly higher UCP3 mRNA expression in both skeletal muscle (3.76 +/- 0.90 vs 8.41 +/- 0.87, P < 0.05) and in adipose tissue (6.38 +/- 0.71 vs 12.48 +/- 1.79, P < 0.05). In vitro studies with adipose tissue fragments indicated that the EGF effect probably is mediated indirectly as incubations with EGF (10 microM) were unable to affect adipose tissue UCP expression, whereas incubations with bromopalmitate stimulated both UCP2 and UCP3 mRNA expression twofold. Thus, EGF treatment in vivo was found to enhance UCP3 mRNA expression in both adipose tissue and skeletal muscle, which may indicate that the EGF effect on body composition might involve up-regulation of UCP3 in skeletal muscle and adipose tissue.

Adipose Tissue↗

PubMed2000

Psychoactive substance use diagnoses among psychiatric in-patients.

OBJECTIVE: To estimate the prevalence and possible under-diagnosing of substance use disorders and to consider factors that might influence diagnosing of substance use disorders. METHOD: Data collected from case records and PSE interviews of psychiatric in-patients from 12 psychiatric departments in Denmark admitted during October 1996 were compared with data from the Danish Psychiatric Register. RESULTS: A substantially lower prevalence of substance use diagnoses were found in the register (26.1%) than in the research data (50.0%). A high prevalence of co-occurrence between substance use disorders and mental disorders other than substance use disorders was found (37.3%). In the majority of cases knowledge of the substance use disorders was present in the case records, although they had not resulted in a diagnosis. CONCLUSION: The under-diagnosis of substance use disorders is due not only to concealed diagnostic signs and symptoms but also to an under-diagnosis by the psychiatrists, in spite of the fact that information on the substance use was accessible.

Adult↗

PubMed2000

Regulation of uncoupling protein (UCP) 2 and 3 in adipose and muscle tissue by fasting and growth hormone treatment in obese humans.

OBJECTIVE: To investigate whether the expression of uncoupling proteins (UCP2 and UCP3) was affected by a very low calorie diet (VLCD) and growth hormone (GH) treatment for 4 weeks. DESIGN: A randomized, placebo-controlled intervention study of VLCD with or without concomitant GH-treatment. SUBJECTS: Seventeen obese women (body mass index, BMI=42.1+/-1.4 kg/m2 (range 31.8-54.5 kg/m2)) treated with VLCD for 4 weeks and randomized to concomitant placebo treatment (n=9) or GH treatment (n=8). MEASUREMENTS: Fat mass and lean body mass were measured by dual-energy X-ray absorptiometry. Energy expenditure (EE) was measured by indirect calorimetry. UCP2 and UCP3 mRNA were measured in adipose tissue and skeletal muscle biopsies before VLCD and after VLCD+/-GH-treatment by reverse transcription polymerase chain reaction (RT-PCR). RESULTS: VLCD treatment resulted in a mean weight loss of 5.23 kg+/-0.8 (P<0.01), a 4.1% decrease in EE (P<0.05) and a 24% decrease in UCP3 mRNA in adipose tissue (P<0.03), whereas adipose tissue UCP2 mRNA and skeletal muscle UCP2 and UCP3 mRNA levels were unchanged. GH-treatment had no effects on EE, changes in body weight or UCP mRNA level. In multiple regression analysis the change in EE caused by VLCD was significantly correlated with changes in adipose tissue UCP2 mRNA (r=0.66, P<0.02) and a tendency towards a significant association with the change in adipose tissue UCP3 mRNA (r=0.45, P=0.09), but not with change in body weight, skeletal muscle UCP2 or UCP3 mRNA levels. CONCLUSION: VLCD for 4 weeks decreased UCP3 mRNA expression in human adipose tissue, whereas GH-treatment had no effect on UCP expression. Multiple regression analysis demonstrated that changes in adipose tissue UCP2 and probably UCP3 mRNA were correlated with the change in EE. These findings indicate that UCPs in adipose tissue in very obese individuals might play a role for the reduction in EE observed during energy restriction.

Absorptiometry, Photon↗

PubMed2000

Interactions between sex steroid hormones and leptin in women. Studies in vivo and in vitro.

OBJECTIVE: To investigate the associations between sex hormones and leptin. In addition, to investigate the direct effect of sex hormones by incubations of human subcutaneous adipose tissue explants, in vitro. DESIGN: Cross-sectional study and an experimental in vitro study. SUBJECTS: 36 women (age, 23-65 y; body mass index, BMI, 19-65 kg/m2) participated in the cross-sectional study. Subcutaneous abdominal biopsies were taken from nine women (age, 28 - 46 y; BMI, 25.5-36.0 kg/m2) for the in vitro study. MEASUREMENTS: Fat distribution parameters (by dual-energy X-ray absorptiometry and anthropometry), sex hormones, leptin and insulin. RESULTS: Leptin correlated significantly with most estimates of adipose tissue mass (r= 0.5 - 0.9, P< 0.05). However, when the study group was divided in three equal groups (non-obese, obese, and very-obese) it revealed that the correlation predominantly was found in non-obese. In simple correlation analysis leptin was significantly associated with estimates of adipose tissue, insulin and several sex hormones. However, in multiple regression analysis only insulin (partial correlation coefficient = 0.55, P < 0.004) and percentage fat mass (partial correlation coefficient = 0.72, P<0.001) were significantly and independently correlated with leptin without any independent effect of sex hormones. These findings were in agreement with the in vitro studies where neither estrogen nor androgens (testosterone or DHT) affected subcutaneous adipose tissue leptin production. Dexamethasone (10nM) stimulated adipose tissue leptin production 3-fold (P < 0.001). CONCLUSION: In regression analysis, where both insulin and measurements of fat mass were taken into account, androgens or estrogens did not independently contribute to the variation in leptin levels. Estrogens and androgens had no direct effects on adipose tissue leptin production in vitro. Thus, the sexual dimorphism evident in serum leptin is not likely to be due to a direct influence of sex hormones on leptin production in females.

Absorptiometry, Photon↗

PubMed2000

Effects of growth hormone administration on protein dynamics and substrate metabolism during 4 weeks of dietary restriction in obese women.

OBJECTIVE: Treatment of obesity with very low calorie diet (VLCD) is complicated by protein loss. We evaluated the effects of coadministration of GH on protein turnover, substrate metabolism, and body composition in VLCD treated obesity. DESIGN AND PATIENTS: Fifteen obese women underwent 4 weeks of very low calorie diet (VLCD) in parallel with GH treatment (n = 7) or placebo (n = 8). MEASUREMENTS: Protein metabolism and total glucose turnover were isotopically assayed. Plasma concentrations of amino acids were determined by an HPLC system. Estimated rates of lipid and glucose oxidation were obtained by indirect calorimetry. Fat free mass was determined by DEXA-scan. RESULTS: Protein breakdown decreased in both groups (tyrosine flux micromol/h): -12% +/- 3 (GH) vs. - 9% +/- 3 (placebo)). Phenylalanine degradation in relation to phenylalanine concentration decreased by 9% in the GH group, whereas an increase of 8% was observed in the placebo group (P = 0.1). Plasma concentrations of several amino acids were significantly decreased in the placebo group, while urea excretion decreased in the GH group. A decrease in FFM was found in placebo treated patients (2.14% +/- 1.9 (GH) vs. - 3.54% +/- 1.6 (placebo), P < 0.05). Rates of lipid oxidation tended to be increased by GH treatment (lipid oxidation (mg/minutes): 79.7 +/- 5.9 (GH) vs. 64.6 +/- 5.9 (placebo), P = 0.1). CONCLUSION: During dietary restriction GH primarily seems to conserve protein by a reduced hepatic degradation of amino acids.

Adult↗

PubMed2000

Regulation of lipoprotein lipase and hormone-sensitive lipase activity and gene expression in adipose and muscle tissue by growth hormone treatment during weight loss in obese patients.

It is well known that growth hormone (GH) treatment reduces fat mass (FM), which presumably is mediated through stimulation of triglyceride breakdown and inhibition of adipose tissue lipoprotein lipase activity (AT-LPL). However, it is unknown which of the 2 GH-regulated pathways are of most importance for the reduction in FM. We investigated the effect of weight loss together with GH treatment on the activity and gene expression of LPL and hormone-sensitive lipase (HSL) in AT and muscle tissue. A very-low-calorie diet ([VLCD] 740 kcal/d) was given to 18 obese women (body mass index [BMI] > 35 kg/m2) and half of them were treated with GH (0.04 IU/kg) for 4 weeks in a randomized double-blind placebo-controlled study. Subcutaneous fat and muscle biopsies were taken before and after 4 weeks. Weight loss after 4 weeks was similar in the 2 groups, with a reduction of 4.5% (placebo) and 4.6% (GH) and a reduction of FM by 7.4% and 9.0% ([NS] nonsignificant). The weight loss resulted in a small and NS reduction of AT-LPL activity by 20% +/- 12% in the placebo group, but in the GH group, AT-LPL was significantly reduced by 65% +/- 8% (P < .01). Muscle LPL (M-LPL) activity was not affected by the weight loss alone, but a significant reduction was observed in the GH group (20.4% +/- 10%, P < .05). AT-HSL activity was significantly enhanced after weight loss, but GH had no additional effect on this minor increment. This is in accordance with the finding that the increment in free fatty acid (FFA) after weight loss was similar in the 2 groups. GH treatment was associated with a significant reduction of high-density lipoprotein (HDL) cholesterol (P < .05). In conclusion, GH significantly inhibited AT-LPL activity but had no additional effect on the hypocaloric-induced loss of FM, indicating that under such circumstances, AT-LPL does not directly regulate adipose tissue mass. GH was not found to have opposite effects on the activity of LPL in adipose tissue and muscle, since GH treatment reduced them both (by 65% and 20%, respectively). The VLCD-induced weight loss was associated with a minor enhanced activity of AT-HSL with no independent effect of GH. Thus, concerning body weight, FM, and lipolytic activity, treatment with GH offers no extra benefits during a VLCD for 4 weeks.

Adipose Tissue↗

PubMed2000

Artifact in bone mineral measurements during a very low calorie diet: short-term effects of growth hormone.

Short-term effects of growth hormone on bone metabolism and soft tissue collagen metabolism during weight loss in obese subjects on a very low calorie diet were investigated in a double-blind, placebo-controlled design. Twenty healthy obese women (BMI between 33 and 45 kg/m(2)) aged 21-48 yr were followed for 8 wk: half received growth hormone. A 740-kcal diet was administered the first 4 wk, followed by a 1200-kcal diet. Lumbar spine BMC, total-body fat mass, total-body lean body mass, total-body BMC, and total-body bone area were measured by dual-energy X-ray absorptiometry along with biochemical markers of bone turnover. Body weight decreased by 5.5% and fat mass by 11.4%. There were no changes in biochemical bone markers in the placebo group despite a marked decrease in BMC (3.1%). Projected total bone area decreased proportional to BMC (r = 0.89) during the weight loss. Growth hormone treatment did not modulate the decrease in lean body mass, body weight, fat mass, or BMC, but increased bone turnover markers. Growth hormone did not change the results concerning BMC, projected bone area, BMD, lean body mass or fat mass. Since 89% of the observed change in BMC could be explained by alterations in projected bone area without changes in biochemical bone markers, it is concluded that a large part of the observed decrease in BMC during weight loss may be due to scanner artifact.

Absorptiometry, Photon↗

PubMed1999

Regulation of leptin by steroid hormones in rat adipose tissue.

We investigated if steroid hormones regulate the secretion and the expression of leptin in female and male rat adipose tissue fragments in vitro. Dexamethasone time and dose-dependently increased the secretion and mRNA expression of leptin with a half-maximal stimulation of approximately 1 nM. A time-course revealed a maximal stimulatory effect of 17 beta-estradiol after 24 hours. In male adipose tissue 17 beta-estradiol increased leptin secretion (32% by 50 nM 17 beta-estradiol, P = 0.07 and 34% by 500 nM 17 beta-estradiol, P < 1780.05) after 24 hours. An additional effect of estrogen was seen in the dexamethasone (50 nM) stimulated cells (38% with 50 nM 17 beta-estradiol, P < 0.05 and 48% by 500 nM 17 beta-estradiol, P < 0.05). Basal secretion of leptin was equal in female and male adipose tissue, whereas the effects of 17 beta-estradiol (50 nM) and dexamethasone were significantly increased in female as compared with male adipose tissue. Progesterone, testosterone, dihydrotestosterone and dehydroepiandrostendione-sulfate neither affected leptin secretion in male nor female adipose tissue in vitro. Furthermore, to investigate the effect of estrogen female rats were ovariectomized (OVX) and the adipose tissue was incubated in vitro and compared with adipose tissue leptin secretion from sham operated rats (SHAM), and with ovariectomized rats treated with 17 beta-estradiol (EST). A decreased basal and dexamethasone-stimulated leptin secretion from OVX rats compared with SHAM rats was found (P < 0.005) whereas 17 beta-estradiol treatment of ovariectomized rats maintained a normal leptin secretion. However, the dexamethasone stimulation was equally increased above basal levels in SHAM, OVX and EST rats (3.7 +/- 1.2, 2.9 +/- 0.8, 4.2 +/- 1.4, NS, ANOVA) respectively.

Adipose Tissue↗

PubMed1999

Epinephrine stimulates human muscle lipoprotein lipase activity in vivo.

Lipoprotein lipase (LPL) is involved in lipoprotein metabolism and nutrient partitioning in both adipose tissue and skeletal muscle, and LPL activity is regulated by various hormones and the nutritional state. However, the action of catecholamines has not been thoroughly investigated in humans. Therefore, the effects of exogenous epinephrine on skeletal muscle LPL (SM-LPL) activity and whole-body lipid oxidation were studied. Muscle biopsies were obtained from eight healthy subjects before, during, and after epinephrine infusion. Somatostatin was infused to suppress endogenous insulin production and insulin was infused at a constant rate to maintain basal insulin levels throughout the study. After an equilibrium period (120 minutes), epinephrine (0.05 microg/kg/min) was infused for another 120 minutes. Epinephrine stimulated SM-LPL activity by 21.8%+/-6.8% above basal levels from 1.44+/-0.25 to 1.69+/-0.28 micromol free fatty acid (FFA)/h/g muscle (P<.02), increased plasma FFA 270% from 0.147 to 0.544 mmol/L (P<.05), and increased lipid oxidation 45% from 4.37 to 6.36 mg/kg/min (P<.05). The increase in SM-LPL activity was positively correlated with the increase in whole-body lipid oxidation (R=.75, P<.05). Finally, lipid oxidation and SM-LPL activity were negatively correlated with whole-body glucose oxidation. Overall, the results demonstrate that epinephrine is able to stimulate SM-LPL activity in humans, and thus may have opposite effects on adipose tissue and SM-LPL activity.

Adrenergic alpha-Agonists↗

PubMed1999

Regulation of leptin by thyroid hormone in humans: studies in vivo and in vitro.

The influence of thyroid hormones on human adipose tissue leptin production and leptin gene expression was investigated in vitro and in vivo. Twelve women received 60 microg triiodothyronine (T3) per day for 7 days, which increased total T3 by 195% (1.78 +/- 0.07 to 5.25 +/- 0.39 mU/L, P < .001), significantly decreased thyrotropin ([TSH] 1.57 +/- 0.40 to 0.03 +/- 0.01 mU/L, P < .01), and increased energy expenditure (1,602 +/- 32 to 1,754 +/- 34 kcal/24 h, P < .05). However, serum leptin did not change (9.36 +/- 1.6 v 8.90 +/- 1.3 microg/L, nonsignificant). Human subcutaneous adipose tissue biopsies from eight healthy women were incubated in vitro as small fragments with T3 in concentrations from 1 to 50 nmol/L. Leptin production was inhibited dose-dependently. After 24 hours of incubation, a T3 concentration of 50 nmol/L reduced basal leptin production by 42% (P < .05) and the stimulated leptin production (dexamethasone 10 nmol/L) by 52% (P < .05). Leptin mRNA expression was measured by a semiquantitative multiplex reverse transcriptase-polymerase chain reaction (RT-PCR) method. Fifty nanomolars T3 decreased basal leptin mRNA expression by 47% compared with controls (P < .001), and the stimulated leptin mRNA expression was reduced to a similar degree (53%). In conclusion, in human adipose tissue, T3 (>20 nmol/L) inhibited leptin production and leptin gene expression in vitro, whereas an elevation of T3 corresponding to a moderate thyrotoxic state (T3 5.25 +/- 0.39 nmol/L) was without any impact on serum leptin levels in vivo.

Adipose Tissue↗

PubMed1999

Differential expression of prostaglandin receptor mRNAs during adipose cell differentiation.

To clarify the molecular basis for the prostaglandin (PG) mediated effects in adipose cells at various stages of their development, expression of mRNAs encoding receptors specific for prostaglandin E2, F2alpha and I2 (i.e. EP, FP, and IP receptors) was investigated in differentiating clonal Ob1771 pre-adipocytes, as well as in mouse primary adipose precursor cells and mature adipocytes. We have further characterized the differential expression of mRNAs encoding three subtypes of the EP receptor, i.e. EP1, EP3, and EP4, and examined the expression of mRNAs encoding the three isoforms (alpha, beta, and gamma) of the EP3 receptor. Altogether the results show that the expression of IP, FP, EP1, and EP4 receptor mRNAs was considerably more pronounced in pre-adipose cells than in adipose cells, mRNAs encoding the alpha, beta, and gamma isoforms of the EP3 receptor were all exclusively expressed in freshly isolated mature adipocytes. These data may indicate that PGI2, PGF2alpha, and PGE2 may interact directly with specific receptors in pre-adipose cells, whose transduction mechanisms are known to affect maturation related changes. In mature adipocytes, however, the equipment of mRNAs encoding the EP3 receptor isoforms is in agreement with the well known effect of PGE2 on adenylate cyclase and lipolysis in mature adipocytes.

Adipocytes↗

PubMed1999

Evidence supporting a direct suppressive effect of growth hormone on serum IGFBP-1 levels. Experimental studies in normal, obese and GH-deficient adults.

It has occasionally been suggested that GH directly suppresses circulating IGFBP-1 levels, although it is generally believed that such an effect is secondary to a GH-induced increase in insulin levels. We present data from several experiments in which the effects of GH on IGFBP-1 could be studied more extensively. In normal subjects (n = 36), an i.v. GH bolus caused a small but significant decrease in plasma IGFBP-1 concentrations without changes in insulin [IGFBP-1 (microgram/l): 2.6 +/- 0.3 (GH) vs 3.2 +/- 0.4 (placebo), P < 0.05]. Conversely, a 28-h somatostatin infusion with and without GH administration during fasting in normal subjects yielded higher IGFBP-1 levels in the non-GH substituted study [50.5 +/- 5.3 (GH-suppression) vs 22.6 +/- 5.6 (GH-substitution), P < 0.01], comparable with an increased concentration of IGFBP-1 during fasting in GH-deficient patients without usual GH substitution [23.4 +/- 7.6 (GH pause) vs 14.1 +/- 4.9 (GH substitution), P < 0.01]. In both fasting studies insulin levels remained stable. During a hypocaloric diet, long-term GH treatment in obesity lead to a significant decline in IGFBP-1 level (2.3 +/- 0.6 vs 1.2 +/- 0.2, P < 0.01), while no changes were found in the placebo group. Again, insulin levels remained equally low in both studies. Finally, a significant rebound increase in IGFBP-1 level in response to insulin induced hypoglycemia was only observed among GH-deficient patients, but not in control subjects, the latter of whom responded to hypoglycemia with a significant increase in serum GH levels [23.2 +/- 7.2 (GHDA) vs 2.5 +/- 0.3 (controls), P < 0.01]. In conclusion, a suppressive effect of GH on IGFBP-1 appears to be unmasked in the presence of low or suppressed insulin levels, making GH a potential regulator of IGF-1 bioactivity in a hitherto unrecognized way.

Adult↗

PubMed1999

Regulation of uncoupling protein-2 and -3 by growth hormone in skeletal muscle and adipose tissue in growth hormone-deficient adults.

The newly described uncoupling proteins, UCP2 and UCP3, may play a role in regulating energy expenditure (EE) in humans. GH deficiency (GHD) is associated with decreased lean body mass, increased adiposity, and reduced EE, which are reversed by GH treatment. In the present study we investigated whether GH treatment for 4 months influenced the expression of UCPs in skeletal muscle and adipose tissue in 22 GHD patients who were investigated before and after GH (n = 11) or placebo (n = 11) treatment. GH treatment increased the amount of lean body mass by 4.5% (P < 0.05) and decreased body fat mass by 12% (P < 0.05), whereas no changes in these parameters were observed after placebo treatment. The level of UCP3 messenger ribonucleic acid (mRNA) increased 3-fold (P < 0.005) in skeletal muscle and almost 2-fold (P < 0.05) in adipose tissue after GH treatment, with no changes observed after placebo treatment. Skeletal muscle UCP2 mRNA was slightly (25%), but significantly (P < 0.05), decreased, whereas the level of UCP2 mRNA in adipose tissue was unaffected after GH treatment. The T4 level was positively correlated with skeletal muscle UCP2 and UCP3 expression (r = 0.518; P < 0.05 and r = 0.463; P < 0.05, respectively). Furthermore, plasma free fatty acids were positively correlated with the expression of UCP2 (r = 0.573; P < 0.01) and UCP3 (r = 0.518; P < 0.05) in skeletal muscle. The marked increase in UCP3 expression after GH treatment indicates that the UCPs might play a role in the effects of GH on EE in GHD patients. Finally, the strong association between thyroid hormone and skeletal muscle UCP and the correlation between plasma free fatty acids and UCP expression in skeletal muscle indicate that these hormones/metabolites might influence UCP expression in humans as previously demonstrated in rodents.

Adipose Tissue↗

PubMed1999

Hormone replacement therapy affects body composition and leptin differently in obese and non-obese postmenopausal women.

Leptin and oestrogen are both involved in the regulation of adipose tissue deposition and feeding behaviour. We investigated whether 5 years of hormone replacement therapy (HRT) affected serum leptin and body composition differently in 89 postmenopausal women treated with HRT compared with 178 controls. At baseline, leptin was significantly correlated with oestradiol (r=0.13, P<0.05) and in multiple backward regression analysis including oestradiol and any estimate of body fat, oestradiol remained a significant determinant of leptin levels. In the control group, all estimates of body fat determined by dual energy X-ray absorptiometry (DEXA) or anthropometry were increased (3.6-16.9%) and leptin increased 31.3% (16.03+/-1.02 to 20.84+/-1.2 ng/ml (s.e.m.), P<0.001). In the HRT group all estimates of body composition also increased during the 5-year observation but to a lesser extent than observed in the control group (1.0-8.5%). Leptin was raised by 19.7% (17.81+/-1.32 to 20.57+/-1.65 ng/ml, P<0.001). However, the DEXA scans revealed that the control group gained 2.4-fold more fat during the 5-year observation (1.9+/-0.3 vs 0.8+/-0.4 kg, P<0.05), and especially the trunk fat increased (1.4+/-0.2 vs 0.7+/-0.3 kg, P<0.05). This was reflected in the increase in leptin levels, which were increased by 7.4% in the control group compared with the HRT group (4.81+/-0.60 vs 2.76+/-0.87 ng/ml, P<0.05). Adjusting for the difference in adipose tissue revealed that HRT had no independent effect on leptin levels. Comparisons between obese (body mass index>25 kg/m(2)) and non-obese (<25 kg/m(2)) subjects by stratifying for HRT treatment using multiple linear regression revealed that the change in fat mass was significantly less among treated subjects (P=0.038) and especially in the non-obese subjects (P=0.001). The change in trunk fat was similarly correlated with treatment status (P=0.029) and with the degree of obesity (P=0.006). In conclusion, 5 years of HRT treatment significantly reduced fat mass accumulation, especially in the trunk region. This effect of HRT was more pronounced in non-obese as compared with obese subjects. The HRT-induced reduction in fat mass seems not to be mediated by leptin.

Body Composition↗

PubMed1999

Effect of growth hormone on adipose tissue and skeletal muscle lipoprotein lipase activity in humans.

Lipoprotein lipase (LPL) is involved in clearing triglyceride-rich chylomicrons and very-low-density lipoprotein particles from the bloodstream, providing free fatty acids to particular adipose tissue for storage and to skeletal muscle tissue for oxidation and energy production. Although the same gene (chromosome 8p22) encodes LPL, the enzyme activity is regulated in a tissue-specific manner. Dysfunction of the LPL enzyme has been implicated in the pathogenesis of dyslipidemia (high triglyceride and low high-density lipoprotein (HDL) cholesterol), early arteriosclerosis, and the pathogenesis of obesity. Treatment with growth hormone (GH) both in vivo and in vitro results in a pronounced reduction (often up to 50%) of LPL activity in adipose tissue in humans. The specific level of messenger ribonucleic acid, however, is not generally affected by GH treatment in adipose tissue, indicating that the effect of GH is mediated at a post-translational level. The GH-mediated reduction in adipose tissue LPL activity may be involved in the reduction in adipose tissue mass commonly seen after prolonged GH treatment in GH-deficient adults and GH treatment in obese subjects. LPL activity in adipose and skeletal muscle tissue is generally regulated in a reciprocal manner by, for example, fasting, feeding, insulin and epinephrine. A high level of LPL activity, particularly in skeletal muscle tissue, has been found to be associated with a beneficial lipoprotein profile (low triglyceride and high HDL cholesterol). In investigations where obese but otherwise healthy women were treated with GH, and in another study where adults with GH deficiency were treated for 4 months with GH, we found no effects of GH on either skeletal muscle LPL activity nor on skeletal muscle LPL gene expression. In conclusion, GH has a pronounced inhibitory effect on adipose tissue LPL activity, which is mediated at a post-translational level. The GH-induced reduction in adipose tissue mass may be partly mediated by this effect on adipose tissue LPL. GH has no effects on LPL activity in skeletal muscle, which may be related to the fact that GH has no or only minor effects on plasma triglyceride and HDL cholesterol levels. Finally, GH is not, unlike for example insulin and catecholamines, involved in antagonistic regulation of LPL in muscle and adipose tissue.

Adipose Tissue↗

PubMed1998

[The auto- and endocrine function of the adipose tissue. Significance for metabolic complications in obesity].

The present review discusses recent research showing adipose tissue to be highly metabolically active, producing and releasing many different bioactive compounds besides free fatty acids (FFA) such as tumor necrosis factor alpha (TNF alpha), leptin, acetylation stimulating protein (ASP), plasminogen activator inhibitor-1 (PAI-1), cholesterol ester transfer protein (CETP), prostaglandins and oestrogens. Most of these compounds have autocrine effects on the adipose cells and they are presumably involved in the physiological regulation of blood flow, growth and metabolism of the adipose tissue. When the adipose tissue becomes enlarged, as seen in association with obesity, it has now been shown that several of the compounds produced in the adipose tissue (TNF, PAI-1, CETP etc.) may be directly involved in the pathogenesis of some of the complications commonly seen in association with obesity such as insulin resistance, hypertension, enhanced thrombogenesis, and premature atherosclerosis.

Adipose Tissue↗

PubMed1998

Serum leptin levels and leptin expression in growth hormone (GH)-deficient and healthy adults: influence of GH treatment, gender, and fasting.

Growth hormone (GH) treatment is associated with a reduction in fat mass in healthy and GH-deficient (GHD) subjects. This is mainly mediated via a direct GH action on adipose cells and stimulation of lipolysis. Leptin is secreted from adipose tissue and may be involved in signaling information about adipose tissue stores to the brain. Hormonal regulation of leptin is still not fully elucidated, and in the present study, we investigated both the long-term (4-month) and short-term (28-hour) GH effects on serum leptin and leptin gene expression in subcutaneous adipose tissue. In GHD adults (n = 24), leptin correlated with most estimates of adiposity (r = .62 to .86), as previously found in healthy subjects. However, no correlation was observed with intraabdominal fat determined by computed tomographic (CT) scan (INTRA-CT). GH treatment for 4 months had no independent effect on either serum leptin or leptin gene expression. In a short-term study, we found that fasting gradually reduced leptin levels in both healthy men and GHD adults, with a maximum reduction of 58% to 60% (P < .01) after 31 hours. No independent effect of GH suppression or GH substitution on serum leptin was found during fasting. Adipose tissue leptin mRNA correlated with serum leptin (r = .51, P < .01) and the body mass index ([BMI] r = .55, P < .05). Serum leptin levels and gene expression were significantly higher in women compared with men (26.6 +/- 5.8 v 10.0 +/- 1.30 ng/mL, P < .05). However, in regression analysis accounting for the gender differences in subcutaneous femoral adipose tissue (FEM-CT), the difference in serum leptin disappeared, indicating that subcutaneous femoral fat or factors closely related to femoral fat (eg, sex hormones) may be causal factors for the gender difference in leptin.

Adipose Tissue↗