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Biomedical subjects

B Richelsen

Publications and source records attributed to B Richelsen.

At least 55 records · Page 3Linked to original sources

Long term follow up of patients who underwent jejunoileal bypass for morbid obesity.

OBJECTIVE: To describe our long term results after jejunoileal (JI) bypass for morbid obesity. DESIGN: Retrospective study. SETTING: Teaching hospital, Denmark SUBJECTS: All 57 patients who underwent JI bypass for morbid obesity between January 1973 and December 1988. INTERVENTIONS: Type A and type B JI bypass. MAIN OUTCOME MEASURES: Weight loss, operative morbidity and mortality, and subjective evaluation of the results. RESULTS: Mean duration of follow up was 15.9 years (range 8-22). There were no operative or early postoperative deaths, but there were 7 late deaths (12%). 5 patients developed postoperative complications (9%), and 11 patients (19%) required reoperation for side effects or complications. The mean body mass index (BMI, kg/m2) was reduced from 47.5 (range 40-60) to 32 (range 22-49) during the follow up period which corresponded to a weight loss of about 42 kg. Of the 39 patients who still had a JI bypass in 1994, nearly two thirds said that they were satisfied with the operation, though they nearly all had some side effects such as diarrhoea or intermittent abdominal pain. CONCLUSION: As complications of JI bypass can develop at any time, we suggest that all patients who have had the operation should be regularly followed up at special clinics so that complications can be diagnosed and treated as soon as possible.

Adult↗

Systemic administration of epidermal growth factor reduces fat mass in rats: effects on the hormone-sensitive-lipase, lipoprotein lipase and leptin.

We examined whether the reduction in fat mass induced by EGF treatment in mature animals was via activation of hormone-sensitive lipase (HSL) and thereby the induction of lipolysis, or through inhibition of lipoprotein lipase activity thus reducing fat uptake in adipose tissue. Sixteen male rats were treated with placebo or EGF 150 microg/kg/day for 7 days via mini-osmotic pumps. The results demonstrate that systemic EGF treatment reduces the amount of adipose tissue, most likely due to increased lipolysis as HSL activity as well as HSL mRNA were increased. The circulating levels of free fatty acids were slightly increased and leptin levels reflected the decrease in adipose tissue mass.

Adipose Tissue↗

Expression of the two isoforms of prostaglandin endoperoxide synthase (PGHS-1 and PGHS-2) during adipose cell differentiation.

Expression of mRNAs encoding the two prostaglandin endoperoxide synthase (PGHS) isoenzymes (PGHS-1 and -2) was investigated in differentiating clonal Ob1771 mouse preadipocytes and in mouse adipose tissues. Northern analysis revealed that the expression level of PGHS-1 mRNA was reduced by 98+/-0.2% (P <0.01) during differentiation of Ob1771 cells, whereas PGHS-2 mRNA was not detected. By reverse transcriptase-polymerase chain reaction analysis, however, both PGHS-1 and -2 mRNA was detected in Ob1771 preadipose cells. In addition. mRNAs encoding both isoforms were markedly expressed in primary adipose precursor cells with considerably lower expression levels in mature adipocytes (56 75% reduction, P<0.01). Furthermore, exposure to dexamethasone (10 nM) for both 24 h (explants of adipose tissue) and 48 h (Ob1771 adipose cells) resulted in enhanced expression of PGHS-1 mRNA. whereas expression of PGHS-2 mRNA in explants of adipose tissue (24 h incubation) was reduced by 83 +/- 9% (P<0.05). In contrast, exposure to angiotensin II (100 nM) enhanced expression of PGHS-1 mRNA both in mature adipocytes (4 h incubation) and explants of adipose tissue (24 h incubation), and elevated PGHS-2 mRNA expression in mature adipocytes (4 h incubation). In conclusion, this report suggests a differential expression of PGHS mRNAs during adipose cell differentiation, and further suggests that the machinery for prostaglandin synthesis in mature adipocytes may be induced by various hormones.

Adipose Tissue↗

Action of growth hormone in adipose tissue.

Growth hormone (GH) has diverse and still not fully elucidated effects on adipose tissue. Both preadipocytes and mature adipocytes possess specific GH receptors. GH may mediate its actions via these receptors, but some effects are indirectly mediated through the GH-mediated secretion of insulin-like growth factor-I (IGF-I). IGF-I may then act back on the adipose tissue in an autocrine/paracrine manner. In primary cultures of adipose precursor cells obtained from human or rat adipose tissue, GH is found to stimulate the proliferation of these immature cells and reduce their differentiation to mature adipocytes. During long-term incubation and in in vivo studies, GH has a pronounced lipolytic effect. Whether this lipolytic effect is a direct effect of GH or more indirectly mediated, for instance, via inhibition of the action of antilipolytic compounds (e.g. adenosine, prostaglandins and insulin) is presently unknown. Finally, GH produces a pronounced inhibition of adipose tissue lipoprotein lipase activity. This enzyme plays a main role for hydrolysing triglycerides in the blood circulation in the adipose tissue and then for triglyceride accumulation in adipose cells. Thus, GH inhibits adipocyte differentiation, reduces triglyceride accumulation and increases lipolyses--all mechanisms which reduce adipose tissue mass.

Adipose Tissue↗

Effects of long-term total fasting and insulin on ob gene expression in obese patients.

In the present study the effect of long-term fasting (6 days) on obese (ob) gene expression was examined in nine severely obese females of 34 +/- 3 years and with a body mass index of 46.4 +/- 2.3 kg/m2. Six days of fasting induced a significant weight loss (126.8 +/- 5.3 vs 120.5 +/- 5.1 kg, P < 0.0001). Insulin-stimulated glucose uptake (hyperinsulinemic, euglycemic clamp, insulin infusion rate 1.5 mU/kg per min) was markedly reduced following fasting (M-value 5.96 +/- 0.74 vs 2.79 +/- 0.23 mg/kg per min, P < 0.0001). Ob mRNA/beta-actin concentration in fat biopsies from abdominal subcutaneous adipose tissue was unchanged after 6 days of fasting (1.50 +/- 0.40 vs 1.47 +/- 0.36 arbitrary units, not significant), whereas serum leptin levels decreased significantly from 53.8 +/- 4.7 to 30.7 +/- 2.0 ng/ml (P < 0.0001) during the same period. No significant correlations were found between insulin-stimulated glucose uptake and serum leptin concentration, either prior to the fast or after the fast. Serum leptin levels were unchanged by hyperinsulinemia for 3 h during the clamp prior to the fast, while hyperinsulinemia for 3 h after 6 days of fasting increased serum leptin by 25% (P < 0.01). In conclusion, 6 days of fasting reduced serum leptin by about 40%. In contrast, ob mRNA in abdominal subcutaneous adipose tissue was unchanged. Furthermore, after 6 days of fasting insulin was able to increase the serum level of leptin significantly, indicating that the effect of insulin on the level of leptin is dependent on the nutritional state.

Adipose Tissue↗

[Significance of fat distribution for metabolic risk factors in healthy males of normal weight].

A homogeneous group of non-obese men (n = 58), all 44 years old, were investigated in order to determine whether body fatness and especially abdominal fatness influence the metabolic risk profile in normal-weighted men. In addition, it was investigated which anthropometric measurements that were most closely associated with the risk profile. It was found that enhancement of total fatness, but particularly even a minor accumulation of the adipose tissue in the abdominal region in these otherwise non-obese men, was associated with a considerably adverse metabolic risk profile. Those risk factors that seemed to be most "sensitive" for abdominal fatness were HDL-cholesterol, the atherogenic index, triglyceride and fasting plasma insulin. The sagittal diameter (SD) seemed to be slightly better correlated to the risk profile than other anthropometric indices of abdominal fatness (e.g. WHR).

Abdomen↗

Changes in adenosine A1- and A2-receptor expression during adipose cell differentiation.

Two adenosine receptors A1 and A2 are associated with either stimulation (A2) or inhibition (A1) of adenylate cyclase. Using the clonal cell line Ob1771, we have studied the expression of the two receptors during the process of adipose conversion accelerated by exposure to dexamethasone and 3-isobutyl-l-methylxanthine (IBMX) during the first 3 days post-confluence. The effects mediated by the two receptors on preadipocyte differentiation and adipocyte metabolism were also investigated. The two adenosine agonists NECA and PIA were used as preferential agonists of the A2- and A1-receptor, respectively. In preadipose cells (just confluent), both of the mouse clonal line and human primary culture, NECA dose-dependently stimulated cAMP production with a significant higher potency (P < 0.01) than did PIA. In adipose cells (16-day post-confluent) NECA was found to exert a biphasic effect on forskolin-stimulated cAMP production: i.e., NECA was clearly inhibitory in the femto- to picomolar concentration range whereas this effect gradually diminished at higher concentrations. The effect of PIA in 16-day post-confluent adipose cells however, was purely inhibitory on both cAMP production (IC50: 33.52 +/- 0.44 fM) and lipolysis (64% +/- 7%; P < 0.01). These findings were corroborated by Northern blot analysis which revealed A1-receptor mRNA to be exclusively expressed in the mature adipocytes, whereas A2-receptor mRNA gradually declined during the differentiation process except in 16-day post-confluent cells. In addition, NECA significantly enhanced the effect of corticosterone-induced differentiation by 46.8% (P < 0.05) but failed to have any adipogenic potency acting either alone or in concert with carbaprostacyclin (cPGI2). Thus, endogenous adenosine may have a bimodal action on adipose tissue metabolism mediated through stimulatory A2- and inhibitory A1-receptors, respectively, as a function of adipose conversion.

1-Methyl-3-isobutylxanthine↗

Identification of oestrogen receptors and oestrogen receptor mRNA in human adipose tissue.

The distribution of adipose tissue has a major impact on the morbidity and mortality associated with obesity. Furthermore, the distribution of adipose tissue seems to be regulated by sex hormones. Controversy exists over whether the effects of sex hormones (oestrogen and testosterone) on human adipose tissue are an indirect or a direct effect as contradictory results have been obtained when investigating the existence of these receptors in human adipose tissue. In the present study the authors reinvestigated the possible existence of oestrogen receptors (ERs) in human adipose tissue. Human adipocytes from both genders were found to contain specific oestrogen binding sites determined by ligand-binding techniques. The binding protein had a molecular weight of 65 kD (which is similar to that of the ER found elsewhere) and it was found that adipocytes contained mRNA encoding the ER. Moreover, human preadipocytes had no oestrogen-binding capacity and did not possess mRNA encoding the ER. Finally, the authors detected regional differences in receptor density. Women had an equal oestrogen-binding capacity in adipose tissue from the subcutaneous abdominal and the visceral depot, whereas men had twice as high oestrogen-binding capacity in subcutaneous adipose tissue compared with adipose tissue in the visceral fat depot. These findings indicate that mature human adipocytes possess ERs and thus, might be an oestrogen-responsive tissue and that oestrogen may be acting directly in mature adipocytes via its specific receptor. Human preadipocytes, however, seemed not to be an oestrogen-responsive tissue. Finally, preliminary data suggest that there might be differences in ER densities in different fat depots.

Abdomen↗

Identification of steroid receptors in human adipose tissue.

Steroids have the ability to alter adipose tissue distribution. Controversy exists as to whether these effects of sex hormones (oestrogen, progesterone and testosterone) on human adipose tissue are indirect or direct, as only very few studies have focused on steroid receptor status in human adipose tissue. In the present study, we reinvestigated steroid receptor status in human mature adipose tissue and human preadipocytes. Oestrogen, glucocorticoid and androgen receptors were found in human mature adipocytes from both women and men. The receptors were detected by ligand binding. Furthermore, the existence of the receptors was confirmed by demonstrating that adipocytes contained mRNA encoding the receptors. cDNA was generated using reverse transcriptase (RT) followed by polymerase chain reaction (PCR) amplification using specific primers (RT-PCR) for the specific steroid receptors. Adipocytes did not contain mRNA encoding the progesterone receptor (PR), and no progesterone binding was detectable in human adipocytes. Human preadipocytes contained glucocorticoid receptor (GR) mRNA and androgen receptor (AR) mRNA, whereas we were unable to detect oestrogen receptor (ER) mRNA and progesterone mRNA in human preadipocytes. In conclusion, oestrogen glucocorticoid and androgen receptors are present in mature adipocytes from subjects of both sexes, whereas adipocytes do not contain progesterone receptors. In preadipocytes, only glucocorticoid receptors and androgen receptors are present, whereas oestrogen receptors and progesterone receptors are not present.

Adipose Tissue↗

Long-term (6 months) effect of a new fermented milk product on the level of plasma lipoproteins--a placebo-controlled and double blind study.

OBJECTIVE: We have recently demonstrated a short-term hypocholesterolemic effect (reduction of 8-10%) of a new fermented milk product taken for 6 weeks (Agerbaek et al, 1995; Richelsen et al, 1993). The present study was undertaken to investigate the more long-term (6 months) effect of this fermented product on the level of lipoproteins. DESIGN: The study was randomized, double-blind, and placebo-controlled, and performed for a period of six months. SUBJECTS: Eighty-seven non-obese and normocholesterolemic females and males, aged 50-70 y old, were included in the study. INTERVENTION: 200 ml of either the fermented milk product or placebo (chemically fermented) were given daily. The test product was fermented with a bacteria culture containing Enterococcus faecium and two strains of Streptococcus termophilus. RESULTS: After one month the total- and LDL-cholesterol were significantly reduced in the fermented milk group as compared to placebo, LDL was reduced by 0.21 mmol/l vs 0.0 mmol/1 (P < 0.02). The maximal reduction of LDL-cholesterol was reached after 3 months in the test group with a reduction of 0.32 mmol/1 of initial values (P < 0.001). In the placebo group a gradual fall of total- and LDL-cholesterol was observed from 1-6 months of the study. Thus, after six months the reduction of LDL-cholesterol was similar in the two groups (P = 0.95) even though the reduction was significant in both groups in relation to initial values (P < 0.05). No changes in HDL-cholesterol or triglyceride were observed during the study. There were no differences in the response between women and men. CONCLUSION: The fermented milk product resulted in a rapid reduction of LDL-cholesterol observed after one month but during long-term intake (6 months) the reduction of LDL-cholesterol was similar to the placebo product, indicating that low-fat milk or fermented milk products may have some hypocholesterolemic effects but the present tested product does not seem to be superior in that respect to the placebo milk product used in the present study.

Aged↗

Inhibition of renal ornithine decarboxylase activity fails to reduce kidney size and urinary albumin excretion in diabetic rats with manifest kidney hypertrophy.

Formation of polyamines has previously been shown to play an important role for initial kidney growth in experimental diabetes, as treatment of diabetic rats with a selective ornithine decarboxylase (ODC) inhibitor, initiated immediately after diabetes induction, abolishes the initial kidney growth. In order to investigate the role of polyamine formation for the maintenance of diabetic kidney hypertrophy, ODC inhibition was initiated after manifest kidney hypertrophy had occurred. The kidney weight in diabetic rats was significantly larger than in control rats after a diabetes duration of 7, 14, 50 and 71 days and the total glomerular volume was increased in kidneys from diabetic rats after a diabetes duration of 71 days. Renal activity of ODC was increased in diabetic rats throughout the study period of 71 days. Treatment of diabetic rats with the selective ODC inhibitor di-fluoro-methyl-ornithine (DFMO) was maintained for two periods (days 7-14 and days 50-71). DFMO treatment had no effect on 24-h food consumption, blood glucose concentration or body weight. However, despite almost total inhibition of the kidney ODC activity, there was no effect on kidney growth or total glomerular volume in the DFMO treated diabetic rats compared to placebo treated diabetic rats. Finally, the urinary albumin excretion was markedly increased in diabetic rats with no effects of ODC-inhibition. In conclusion, inhibition of ODC initiated in diabetic rats with manifest kidney enlargement had no effect on renal size, glomerular volume or urinary albumin excretion. These findings together with our previous findings indicate that the role of polyamines in diabetic kidney enlargement is restricted to the first week after diabetes induction.

Albuminuria↗

Serum concentrations of insulin-like growth factors (IGFs), IGF binding proteins 1 and 3 and growth hormone binding protein in obese women and the effects of growth hormone administration: a double-blind, placebo-controlled study.

Obesity is associated with suppressed growth hormone (GH) concentrations but relatively little is known about insulin-like growth factors(IGFs) and binding proteins for GH and IGFs (GHBP and IGFBPs) and the modulatory effect of GH administration. In a double-blind, crossover design we studied the impact of 5 weeks of placebo or GH administration (0.03 mg.kg-1 body wt.day-1) in nine obese women (mean +/- SEM: age 30.4 +/- 2.4 years; body mass index 37.0 +/- 2.8 kg/m2) on IGF-I, IGF-II, IGFBP-1 and -3 and GHBP. Serum IGF-I (microgram/l) levels were subnormal and increased significantly following GH (117 +/- 16 (placebo) vs 434 +/- 33 (GH) vs 198 +/- 15 (control (p < 0.01)). By contrast, serum IGF-II (microgram/l) levels were in the normal range and remained unchanged (608 +/- 20 (placebo) vs 647 +/- 40 (GH) (NS)). Serum IGFBP-3 was in the normal range and increased significantly during GH treatment, although relatively less than IGF-I, such that the molar ratio between IGF-I and IGFBP-3 increased with GH treatment, whereas the ratio between IGF-I + IGF-II and IGFBP-3 remained unchanged. Serum IGFBP-1 was low in the placebo situation but became further and almost completely suppressed during GH treatment. During a 2-h hyperinsulinemic, euglycemic glucose clamp, IGFBP-1 decreased in the placebo study and remained suppressed during GH. Serum GHBP (nmol/l) levels were elevated substantially compared to non-obese controls (p < 0.001) and did not change during GH treatment (2.37 +/- 0.36 (placebo) vs 2.21 +/- 0.25 (GH) vs 0.80 +/- 0.19 (control)).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Relationship between sex hormones, body composition and metabolic risk parameters in premenopausal women.

The metabolic complications associated with obesity are dependent upon the degree of obesity and the distribution of adipose tissue. In order to evaluate the associations between sex hormone status, metabolic risk parameters, obesity and distribution of adipose tissue, 25 premenopausal women with a wide range of body mass index (19.3-48.1 kg/m2 were studied. Body composition was determined by dual-energy x-ray absorptiometry scan and anthropometric measurements; in addition, lipid and sex hormone status were determined and an oral glucose tolerance test was performed. We found that sex hormone-binding globulin was correlated negatively with total fat mass (r = -0.77, p < 0.001) and especially with abdominal localization of adipose tissue (r = -0.85, p < 0.001). Free testosterone was correlated positively with total fat mass (r = 0.40, p < 0.05) and with abdominal fat accumulation (r = 0.64, p < 0.001). Free estrogen was correlated negatively with total amount of adipose tissue (r = -0.40, p < 0.05) but not with the distribution of adipose tissue. Finally, total fatness, abdominal localization of adipose tissue and free testosterone were all associated with elevated metabolic risk factors. However, multiple regression analysis revealed that only abdominal localization of adipose tissue was independently associated with a higher risk profile, whereas the effects of sex hormones or total fatness disappeared when abdominal localization of adipose tissue was included in the analysis. In conclusion, these findings in premenopausal women indicate that the connection between sex hormones and metabolic risk factors might be indirect, probably operating through alterations in the amount of adipose tissue in the abdominal region.

Adipose Tissue↗

Hypocholesterolaemic effect of a new fermented milk product in healthy middle-aged men.

OBJECTIVE: There are still controversies as to the potential beneficial effects of milk and fermented milk products on the level of lipoproteins. The objective of the present investigation was to test the effect of a moderate daily intake of a new fermented milk product, which was based on a bacterial culture obtained from the intestinal flora of inhabitants of Abkhasia, on the lipoprotein levels of a homogeneous group of middle-aged Danish men. DESIGN: The study was randomised, double-blind, and placebo-controlled, and the intervention was performed for a period of 6 weeks. SUBJECTS: Fifty-eight healthy, non-obese, normocholesterolaemic, male volunteers born in 1949 of Danish descent participated (i.e. all were 44 years old). INTERVENTIONS: During the intervention period the subjects' habitual diets were supplemented with 200 ml/day of either the new fermented milk product or a placebo product (chemically fermented). The biologically fermented milk product contained Enterococcus faecium and two strains of Streptococcus termophilus. Fasting blood samples were drawn initially and after 3 and 6 weeks and analysed for plasma values of total cholesterol, high-density lipoprotein (HDL)-cholesterol and triglyceride. In addition, LDL-cholesterol was estimated. RESULTS: After these 6 weeks total cholesterol was reduced significantly in the group given biologically fermented milk (-0.37 mmol/l, confidence interval: -0.51 to -0.23) while no changes were observed in the placebo group (-0.02 mmol/l) (P < 0.01). This reduction in total cholesterol could be completely ascribed to a fall in LDL-cholesterol by 10% (i.e. -0.42 mmol/l) since HDL-cholesterol and triglyceride were unchanged in both groups. CONCLUSIONS: Thus, this short-term study (6 weeks) demonstrated an LDL-cholesterol-lowering effect (10% reduction) of a new fermented milk product in middle-aged Danish men.

Adult↗