Objective: Polycystic ovary syndrome (PCOS) patients are abdominally obese and are at increased risk of developing the metabolic syndrome. Low adiponectin and ghrelin levels in PCOS patients could be caused by insulin resistance as well as high testosterone levels. Design: Adiponectin and ghrelin levels were evaluated in 51 hirsute PCOS patients referred to the outpatient clinic of an academic, tertiary care medical centre and in 63 weight-matched female controls. Relationships between adiponectin, ghrelin, leptin, body composition, testosterone and insulin were examined. Methods: Measurements of body composition including waist-hip-ratio (WHR), body mass index (BMI) and whole body dual-energy X-ray absorptiometry scan measures of body fat mass. Measurements of fasting levels of adiponectin, ghrelin, leptin, androgen status, oestradiol, lipid variables and insulin during follicular phase. Results: Adiponectin levels were significantly decreased in obese PCOS patients compared with weightmatched controls (geometric mean (K2 to 2 S.D.) 5.3 (2.5-11.1) vs 7.3 (3.0-17.4) mg/l, P!0.05). Mean ghrelin was significantly lower in hirsute PCOS patients than in controls (0.6 (0.3 to 1.4) vs 0.8 (0.4 to 1.7) mg/l, P!0.001) and this remained significant after subdividing subjects according to waist circumference and BMI. During multiple regression analysis, testosterone correlated positively with adiponectin and negatively with ghrelin independent of BMI, WHR and total fat mass. Conclusion: Obese hirsute PCOS patients demonstrated significantly lower adiponectin levels than weight-matched controls suggesting a very high risk for the metabolic syndrome. Furthermore, ghrelin levels were decreased in hirsute PCOS patients and showed a significant, negative correlation with testosterone independent of body composition.European Journal of Endocrinology 155 337-345

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Hulstrøm V, Prats C, Vinten J. Adipocyte size and cellular expression of caveolar proteins analyzed by confocal microscopy. Am J Physiol Cell Physiol 304: C1168 -C1175, 2013. First published April 10, 2013 doi:10.1152/ajpcell.00273.2012.-Caveolae are abundant in adipocytes and are involved in the regulation of lipid accumulation, which is the main volume determinant of these cells. We have developed and applied a confocal microscopic technique for measuring individual cellular expression of the caveolar proteins cavin-1 and caveolin-1 along with the size of individual adipocytes. The technique was applied on collagenase isolated adipocytes from ad libitum fed Sprague-Dawley rats of different age (4-26 wk) and weight (103-629 g). We found that cellular expression of caveolar proteins was variable (SD of log expression in the range from 0.25 to 0.65). Regression analysis of protein expression on adipocyte size revealed that the expression of the caveolar proteins cavin-1 and caveolin-1 on adipocytes from individual rats was tightly related to adipocyte cell surface area (mean coefficient of regression was 0.83 for cavin and 0.77 for caveolin), indicating that caveolar density was the same in membranes from all cells within a biopsy. This intrinsic relation remained unchanged with animal age, but adipocytes from animals with increasing age showed a decrease in mean expression of caveolar proteins per unit cell surface. The different relation between adipocyte size and cellular expression levels of caveolar proteins within and between individuals of different age shows that caveolar density is an age-sensitive characteristic of adipocytes.adipocyte cell size; caveolae; cavin-1; caveolin-1 MEAN ADIPOCYTE SIZE AND ADIPOSE tissue cellularity increases with age in sedentary inbred rodents. Furthermore, it is well documented that obesity is associated with decreased insulin sensitivity of fat cells (6, 40). Many research groups have studied the relationship between a number of metabolic parameters and adipocyte size (8,11,15,35). Early studies of possible functional impacts of adipocyte size were carried out on pools of cells from animals of different age or weight and consequently different mean cell size (29,30,36). Interpretation of data from such studies is difficult since it is not possible to dissociate an influence of cell size per se from an effect of interindividual factors correlated to cell size during aging. To analyze whether the functions of the fat cell vary with adipocyte size per se, it is necessary to separate fat cells of different sizes in the same biopsy. Techniques from the early 1970s took advantage of differences in flotation rates of small and large adipocytes (1) or fractionation of adipocytes by filtering the adipocyte suspension through nylon mesh screens of different pore size (13) subdividing isolated fat cells in populations with different mean diameters. Those studies showed that both basal and insulin-stimulated glucose metabolism increase with cell size so that the insulin fold response...

Patients with type 2 diabetes (T2D) and their first-degree relatives (FDRs) are characterized by hypoadiponectinaema and insulin resistance. In T2D patients, plasma adiponectin and insulin sensitivity (SI) increase in response to thiazolidinediones (TZDs). These findings suggest a role for adiponectin in the regulation of SI. We studied the relationship between plasma adiponectin and glucose and lipid metabolism and the effect of troglitazone (200 mg/day) for 12 weeks in 19 normoglycaemic, obese FDR and 20 obese T2D patients, using euglycaemic-hyperinsulinaemic clamps, glycolytic flux calculations and indirect calorimetry. Plasma adiponectin was similar in both groups, despite higher glucose disposal (Rd), glucose oxidation and glycolytic flux and lower lipid oxidation during insulin stimulation in FDR compared with T2D patients. Plasma adiponectin correlated with insulin-stimulated Rd, non-oxidative glucose disposal (NOGD), glucose storage and SI in both groups after adjustment for sex and body fat. The troglitazone-mediated upregulation of plasma adiponectin was associated with increased insulin-stimulated Rd, NOGD and glucose storage in both groups. No effect on endogenous glucose production was observed. In FDR, plasma adiponectin correlated with insulin-stimulated glycogen synthase activity and the troglitazone-induced increase in plasma adiponectin correlated with the improvement in insulin-stimulated Rd and SI after adjustment for sex and body fat. In conclusion, plasma adiponectin in weight-matched FDR and T2D patients is comparably low and correlates with insulin-mediated glucose uptake and storage. Moreover, these data provide evidence for an adiponectin-dependent insulin-sensitizing effect of TZDs at an early stage before development of T2D and that this effect is exerted mainly on insulin-mediated glucose metabolism.

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