Fat depot-specific impact of visceral obesity on adipocyte adiponectin release in women.

Our objective was to examine omental and subcutaneous adipocyte adiponectin release in women. We tested the hypothesis that adiponectin release would be reduced to a greater extent in omental than in subcutaneous adipocytes of women with visceral obesity. Omental and subcutaneous adipose tissue samples were obtained from 52 women undergoing abdominal hysterectomies (age: 47.1 +/- 4.8 years; BMI: 26.7 +/- 4.7 kg/m(2)). Adipocytes were isolated and their adiponectin release in the medium was measured over 2 h. Measures of body fat accumulation and distribution were obtained using dual-energy X-ray absorptiometry and computed tomography, respectively. Adiponectin release by omental and subcutaneous adipocytes was similar in lean individuals; however, in subsamples of obese or visceral obese women, adiponectin release by omental adipocytes was significantly reduced while that of subcutaneous adipocytes was not affected. Omental adipocyte adiponectin release was significantly and negatively correlated with total body fat mass (r = -0.47, P < 0.01), visceral adipose tissue area (r = -0.50, P < 0.01), omental adipocyte diameter (r = -0.43, P < 0.01), triglyceride levels (r = -0.32, P < or = 0.05), cholesterol/high-density lipoprotein (HDL)-cholesterol (r = -0.31, P < or = 0.05), fasting glucose (r = -0.39, P < or = 0.01), fasting insulin (r = -0.36, P < or = 0.05), homeostasis model assessment index (r = -0.39, P < or = 0.01), and positively associated with HDL-cholesterol concentrations (r = 0.33, P < or = 0.05). Adiponectin release from subcutaneous cells was not associated with any measure of adiposity, lipid profile, or glucose homeostasis. In conclusion, compared to subcutaneous adipocyte adiponectin release, omental adipocyte adiponectin release is reduced to a greater extent in visceral obese women and better predicts obesity-associated metabolic abnormalities.

Effect of a six-week national cholesterol education program step 1 diet on plasma sex hormone-binding globulin levels in overweight premenopausal women.

BACKGROUND: Low circulating sex hormone-binding globulin (SHBG) concentrations have been associated with the presence of several features of the metabolic syndrome in both men and women. Nutritional factors including dietary lipids and fibers in particular have been suggested to modulate plasma SHBG levels. METHODS: The primary objective of the present study was to investigate the effect of an oat bran-rich supplement in conjunction with the National Cholesterol Education Program (NCEP) Step 1 diet (< 30% of total energy from fat, < 10% of energy from saturated fat, and < 300 mg cholesterol per day) on plasma SHBG levels in 35 overweight premenopausal women. Subjects (age 38.6 +/- 7.4 years) had normal menstrual cycles and were tested in the midluteal phase. Since no effect of the oat bran supplement was observed on plasma SHBG levels, data were analyzed according to the 6-week NCEP Step 1 diet. RESULTS: The NCEP Step 1 nutritional intervention caused a significant decrease in energy intake ( -11%, p < 0.05), percent fat intake (-10%, p < 0.005), as well as saturated (-20%, p < 0.005) and monounsaturated (-10%, p < 0.05) fatty acid intake. Body mass index (BMI) decreased slightly but significantly (from 29.2 +/- 4.5 to 28.8 +/- 4.3 kg/m(2), p < 0.005). Plasma SHBG levels increased significantly (from 70.6 +/- 17.7 to 79.9 +/- 15.3 pmol/L, p < 0.0005) following the 6-week NCEP Step 1 diet, whereas plasma insulin levels were not modified significantly. Significant correlations were observed between the change in plasma SHBG levels and baseline BMI (r = 0.36, p < 0.04), as well as baseline (r = -0.42, p < 0.05) and postintervention (r = -0.35, p < 0.05) HDL cholesterol levels. CONCLUSIONS: We observed that a 6-week NCEP Step 1 diet significantly increased plasma SHBG levels, despite the finding that fasting insulin was not modified. Further studies are needed to elucidate physiological mechanisms underlying a direct effect of dietary composition on SHBG production by the liver.

Omental and subcutaneous adipose tissue steroid levels in obese men.

We examined plasma and fat tissue sex steroid levels in a sample of 28 men aged 24.8-62.2 years (average BMI value of 46.3 +/- 12.7 kg/m(2)). Abdominal adipose tissue biopsies were obtained during general or obesity surgery. Omental and subcutaneous adipose tissue steroid levels were measured by gas chromatography and chemical ionization mass spectrometry after appropriate extraction procedures. BMI and waist circumference were negatively correlated with plasma testosterone (r = -0.49 and -0.50, respectively, p < 0.01) and dihydrotestosterone (r = -0.58 and -0.56, respectively, p < 0.01), and positively associated with estrone levels (r = 0.64 and 0.62, respectively, p < 0.001). Regional differences in adipose tissue steroid levels were observed for dihydrotestosterone (p < 0.005), androstenedione (p < 0.0001) and dehydroepiandrosterone levels (p < 0.05), which were all significantly more concentrated in omental versus subcutaneous fat. Positive significant associations were found between circulating level of a steroid and its concentration in omental and subcutaneous adipose tissue, for estrone (r = 0.72 and 0.57, respectively, p < 0.01), testosterone (r = 0.66 and 0.58, respectively, p < 0.01) and dihydrotestosterone (r = 0.58 and 0.45, respectively, p < 0.05). Positive correlations were observed between plasma dehydroepiandrosterone-sulfate and omental (r = 0.56, p < 0.01) as well as subcutaneous adipose tissue dehydroepiandrosterone level (r = 0.38, p = 0.05). Positive significant associations were found between omental adipocyte responsiveness to positive lipolytic stimuli (isoproterenol, dibutyryl cyclic AMP and forskolin) and plasma or omental fat tissue androgen levels. In conclusion, although plasma androgen or estrogen levels are strong correlates of adipose tissue steroid content both in the omental and subcutaneous fat depots, regional differences may be observed. Androgen concentration differences in omental versus subcutaneous adipose tissue suggest a depot-specific impact of these hormones on adipocyte function and metabolism.

Regional differences in adipose tissue metabolism in women: minor effect of obesity and body fat distribution.

Studies comparing adipose tissue metabolism in central versus peripheral fat depots have generated equivocal data. We examined whether regional differences in abdominal subcutaneous and omental adipose tissue metabolism in women exist and whether they persist across the spectrum of body fatness and abdominal adiposity values. We measured adipocyte size; lipoprotein lipase (LPL) activity; and basal, isoproterenol-, forskolin-, and dibutyryl cAMP-stimulated lipolysis in adipose tissue or mature adipocytes isolated from the omental and subcutaneous fat depots in a sample of 55 healthy women undergoing elective gynecological surgery. Measures of body fat mass and body fat distribution were also obtained by dual-energy X-ray absorptiometry and computed tomography. Subcutaneous adipocytes were significantly larger than omental adipocytes (P < 0.0001). LPL activity expressed as a function of cell number was significantly higher in subcutaneous versus omental adipose tissue (P < 0.0001). Basal, isoproterenol-stimulated, dibutyryl cAMP-stimulated (10(-3) mol/l) and forskolin-stimulated (10(-5) mol/l) lipolysis (expressed as a function of cell number) were all significantly higher in subcutaneous versus omental adipocytes (P < 0.05 to P < 0.0001). However, the response of omental adipocytes to lipolytic stimuli tested (fold increase over basal level) was significantly greater in magnitude compared with subcutaneous adipocytes (P < 0.01). These differences were relatively constant across total body fat mass and visceral adipose tissue area tertiles. In conclusion, compared with adipocytes from the omental fat compartment, subcutaneous adipocytes are larger, have higher LPL activity, and are more lipolytic on an absolute basis, which may reflect a higher fat storage capacity in this depot in women. In contrast, omental adipocytes display greater relative responsiveness to both adrenergic receptor-and postreceptor-acting agents compared with subcutaneous adipocytes. Overall and visceral obesity have only minor effects on regional differences in adipose tissue metabolism.

Severe and resistant hypoglycemia associated with concomitant gatifloxacin and glyburide therapy.

Severe and resistant hypoglycemia occurred in two patients with diabetes mellitus who were receiving concomitant gatifloxacin and glyburide. An 84-year-old woman treated with glyburide for type 2 diabetes mellitus experienced, for the first time, a severe episode of hypoglycemia after 2 days of gatifloxacin 400 mg/day for nonproductive cough. Her blood glucose level on hospital admission was 28 mg/dl. Gatifloxacin and glyburide were discontinued, and the patient was treated with intravenous dextrose infused over 36 hours. Glyburide was restarted before her discharge, with no recurrence of hypoglycemia. A 79-year-old man with type 2 diabetes mellitus treated with glyburide was prescribed gatifloxacin 400 mg/day for pneumonia. After 1 day of therapy, the patient was admitted to the emergency department in a coma. His blood glucose level was 18 mg/dl. Despite discontinuation of gatifloxacin and oral hypoglycemic therapy, hypoglycemia was reversed only after administration of multiple boluses of intravenous dextrose, followed by intravenous dextrose infused over 48 hours. On hospital day 7, gliclazide and levofloxacin were started; the patient experienced no recurrence of hypoglycemia and was discharged on day 10. Several cases of severe and resistant hypoglycemia associated with gatifloxacin therapy have been reported in the recent literature. Although the exact mechanism is not fully understood, it may be linked to a gatifloxacin-induced closing of the adenosine 5'-triphosphate-sensitive potassium channels in the pancreatic beta cells, leading to insulin secretion. The onset of hypoglycemia in relation to the start of gatifloxacin suggests that the drug precipitated this adverse event. Patients receiving oral hypoglycemic agents are at greater risk of experiencing gatifloxacin-induced hypoglycemia than patients not receiving these agents. Clinicians should be aware of this potentially life-threatening adverse event and monitor blood glucose levels in all patients receiving concomitant oral hypoglycemic agents and gatifloxacin.

Local androgen inactivation in abdominal visceral adipose tissue.

We examined the expression and activity of two enzymes from the aldoketoreductase (AKR) family 1C, namely type 5 17beta-hydroxysteroid dehydrogenase (17beta-HSD-5, AKR1C3) and type 3 3alpha-hydroxysteroid dehydrogenase (3alpha-HSD-3, AKR1C2) in female sc and omental adipose tissue and in preadipocyte primary cultures. 17beta-HSD-5 preferentially synthesizes testosterone from the inactive adrenal precursor androstenedione, whereas 3alpha-HSD-3 inactivates dihydrotestosterone. mRNAs of both enzymes were detected in adipose tissue from the omental and sc compartments. Real-time PCR quantification indicated a 3-fold higher 3alpha-HSD-3 expression compared with 17beta-HSD-5, and the expression of both enzymes tended to be higher in the sc vs. the omental depot. Accordingly, dose-response and time-course experiments performed in preadipocyte primary cultures indicated that 3alpha-HSD activity was higher than 17beta-HSD activity (13-fold maximum velocity difference). We measured 3alpha-HSD activity in omental and sc adipose tissue samples of 32 women for whom body composition and body fat distribution were evaluated by dual-energy x-ray absorptiometry and CT, respectively. We found that androgen inactivation in omental adipose tissue through 3alpha-HSD activity was significantly higher in women with elevated vs. low visceral adipose tissue accumulation (1.7-fold difference; P < 0.05). Moreover, omental adipose tissue 3alpha-HSD activity was positively and significantly associated with CT-measured visceral adipose tissue (r = 0.43; P < 0.02) and omental adipocyte diameter (r = 0.42; P < 0.02). These results indicate that local androgen inactivation is a predominant reaction in female abdominal adipose tissue, with the greatest conversion rates observed in the presence of abdominal visceral obesity. Increased androgen inactivation in omental adipose tissue of abdominally obese women may impact locally on the regulation of adipocyte metabolism.