Per Björntorp

Cortisol secretion in relation to body fat distribution in obese premenopausal women

Urinary cortisol output and serum cortisol concentrations were measured in the steady state, under field conditions, and during standardized inhibitory and stimulatory tests in premenopausal, obese women, and were analyzed in relation to adipose tissue distribution. Urinary cortisol output was increased under field conditions in women with an elevated waist to hip circumference ratio (WHR) and, in particular, in women with a large abdominal sagittal diameter, indicating visceral fat accumulation. However, dexamethasone inhibition of cortisol secretion was normal. Stimulation with corticotropin analogue and with physical (cold-pressor test) or mental (color-word or mathematic) stress tests also showed elevated responses of serum cortisol, but not of prolactin or growth hormone concentrations. It is suggested that women with visceral fat accumulation have elevated cortisol secretion due to an increased sensitivity along the hypothalamic-pituitary-adrenal axis, and that this may be causing their abnormal fat depot distribution.

Fat cell metabolism in different regions in women. Effect of menstrual cycle, pregnancy, and lactation.

Adipose tissue lipolysis and lipoprotein lipase (LPL) activity were studied in biopsies from the femoral and abdominal depots in healthy women during early or late menstrual cycle, pregnancy, and the lactation period. When the differences in cell size were taken into account, basal lipolysis was similar in both regions in nonpregnant women. During lactation, however, lipolysis was significantly higher in the femoral region. The lipolytic effect of noradrenaline (10(-6) M) was significantly less in the femoral region in the nonpregnant women and during early pregnancy. However, the lipolytic response was the same in both regions in lactating women. LPL activity was higher in the femoral than in the abdominal region except during lactation when a marked decrease in the LPL activity was seen in the femoral region. The LPL activity in the abdominal region remained unchanged in all patient groups. The results imply that in both nonpregnant and pregnant women lipid assimilation is favored in the femoral depot. During lactation, however, the metabolic pattern changes; the LPL activity decreases and lipid mobilization increases in this depot. These changes are much less pronounced in the abdominal region. Thus, fat cells from different regions show a differential response during pregnancy and lactation. These results suggest that the adipose tissue in different regions may have specialized functions.

Hypothalamic arousal, insulin resistance and Type 2 diabetes mellitus

Aims Type 2 diabetes mellitus (DM) develops when insulin resistance overcomes the capacity of compensatory insulin secretion. Insulin resistance may be induced via psychoneuroendocrine pathways, a possibility which has received little previous attention.

Risk factors for Type 2 (non-insulin-dependent) diabetes mellitus. Thirteen and one-half years of follow-up of the participants in a study of Swedish men born in 1913

SummaryThis report presents data on antecedents of Type 2 (non-insulin-dependent) diabetes mellitus in a homogeneous sample of randomly selected 54-year-old men from an urban Swedish population with a diabetes incidence of 6.1% during 13.5 years of follow-up. The increased risk leading to diabetes for those in the top quintile compared to the lowest quintile of the distribution of statistically significant risk factors were: body mass index = 21.7, triglycerides = 13.5, waist-to-hip circumference ratio = 9.6, diastolic blood pressure = 6.7, uric acid = 5.8, glutamic pyruvic transaminase = 3.9, bilirubin = 3.2, blood glucose = 2.7, lactate = 2.4 and glutamic oxaloacetic transaminase = 2.0. Those with a positive family history of diabetes had 2.4-fold higher risk for developing diabetes than those without such a history. In a multivariate analysis glutamic pyruvic transaminase, blood glucose, body mass index, bilirubin, systolic blood pressure, uric acid and a family history of diabetes were all significantly associated with the development of diabetes. Our study demonstrates the great importance of adiposity and body fat distribution for the risk of diabetes. A number of established risk factors for coronary heart disease are risk factors for diabetes as well. Disturbed liver function and increased levels of lactate are early risk factors for diabetes — presumably indicators of the presence of impaired glucose tolerance and/or hyperinsulinaemia.

Number and size of adipose tissue fat cells in relation to metabolism in human obesity

Abstract Body fat and adipose tissue fat cell size and number were determined in a group of obese patients and in controls. These variables were analyzed at different degrees of obesity and compared with metabolic variables, including blood glucose and plasma insulin during glucose tolerance testing and blood lipids. Fat cell size was responsible for the increase of obese adipose tissue at a moderate degree of obesity. With more severe obesity, fat cell number becomes increasingly important and dominates as a factor contributing to obesity. Under conditions of unrestricted diet and activity, plasma insulin correlated positively with fat cell size but not with body fat, and tended to show a negative correlation with fat cell number. The factor in adipose tissue associated with plasma insulin increase is thus probably the fat cell size. The results suggest two forms of obesity. One is characterized by a hypertrophy of fat cells and is of a moderate degree (hypertrophic obesity). This type of obesity is associated with metabolic disturbances. Increased fat cell size might not be a primary factor in this form of obesity, but rather another symptom of metabolic disturbance. The other form (hyperplastic obesity) has an increased number of fat cells and is associated with much more severe obesity, particularly since fat cell size is often increased also in these patients.

Metabolism of mammary, abdominal, and femoral adipocytes in women before and after menopause

In 23 women before and 11 after menopause, adipocyte size, lipoprotein lipase activity, and lipolytic responsiveness to norepinephrine were compared in different regions of adipose tissue. In premenopausal women femoral adipocytes were characterized by a higher lipoprotein lipase activity than abdominal or mammary adipocytes. On the other hand, lipolytic responsiveness and sensitivity in the latter two was higher than in femoral tissue. In postmenopausal women no differences in lipoprotein lipase or lipolysis were found among the three regions. Consequently, menopause in women seemed to be associated with a diminution of not only the increased lipoprotein lipase activity of femoral adipocytes, but also of the high lipolytic response in abdominal and mammary adipose tissue. It is therefore suggested that female sex steroid hormones exert regionally specific effects, ie, increasing lipoprotein lipase in femoral adipocytes, which therefore become enlarged. It also seems possible that stimulation of lipolysis in abdominal and mammary adipocytes is an effect of sex steroid hormones. From the results obtained it is hypothesized that the secondary sex characteristics of adipose tissue distribution in women might be caused by regionally specific effects of sex steroid hormones on adipocyte metabolism.

Development of brown fat cells in monolayer culture: I. Morphological and biochemical distinction from white fat cells in culture☆

The ability of cells from the stromal-vascular fraction of rat brown adipose tissue to develop into adipocytes in primary cell cultures was investigated. Comparison was made with precursor cells isolated by the same procedure from the white adipose tissue of the same animals and cultured in parallel under identical conditions. The culture procedure used allowed the cells isolated from both tissues to rapidly proliferate and differentiate. During the first week in culture the brown fat cells grew to confluence and accumulated fat in a multilocular way. During the second week, further fat was accumulated, but the cells remained multilocular. Analysis of the parallel white fat cell cultures revealed clear differences between the two adipocyte types, although the rates of cell growth were identical. Measurement of the size of the cellular lipid inclusions as a function of the time in culture indicated a much higher number of fat droplets larger than 30 micron in the white adipocytes. Moreover, after isolation of pelleting fractions of both cultured cell types, comparative functional analysis of their mitochondria by oxygen consumption measurement, as well as direct cytochrome-c-oxidase determinations, showed a significantly higher amount of mitochondria in the brown fat cell fractions than in the white fat cell fractions. It was concluded that mature brown fat contains precursor cells which can proliferate and develop into adipocytes in monolayer cell culture and which have inherent characteristics distinct from those of white fat precursor cells.

Cellularity in different regions of adipose tissue in young men and women

Abstract Body cell mass, body fat, and total number of fat cells were determined in young men and women. In addition, regional determinations of adipose tissue thickness, fat cell size, and fat cell number were also performed. The individuals studied were 11 male and 12 female medical students with a mean age of 22 yr. In order to avoid deviations from ideal body weights, the individuals were preselected by using anthropometric standards. The women had more body fat than the men, which was due to an increase in the total number of fat cells. Mean fat cell size did not differ significantly between sexes. The women had greater adipose tissue thickness than the men, which was primarily due to an increase in local fat cell number in all regions investigated (epigastric, hypogastric, femoral, and gluteal) except in the gluteal region, where the difference was mainly explained by larger fat cells in women. When expressed in per cent of maximum values, the intrasexual patterns of adipose tissue thickness and local fat cell number in different regions were similar in men and women, while the pattern concerning fat cell size was slightly different between the sexes. There were no differences between sexes in cholesterol, triglyceride, fasting blood sugar, or fasting insulin values. Middle-aged randomly selected men and women examined previously had a larger amount of body fat than the young men and women, respectively, examined in the present investigation. This difference in body fat with age was due to a larger mean fat cell size in the middle-aged populations, while there was no difference in total fat cell number.

Metabolic Activity of Skeletal Muscle in Patients with Peripheral Arterial Insufficiency

Abstract. 18 patients with intermittent claudication were studied to find some explanation for the beneficial effect of physical training on their symptoms. The patients were randomly allocated to a training group and a placebo‐treated control group. The effect of treatment on serum lipids, muscle lipids and glycogen, walking tolerance, calf blood flow, muscle succinic oxidase activity and the in vitro incorporation rate of glucose‐carbon into various metabolites were studied.

Body fat and adipose tissue cellularity in infants: a longitudinal study.

Body fat, fat cell size, and fat cell number were determined in a longitudinal study on 16 normal-weight infants during the age period 1-18 mo. The methods used included whole-body counting of 40K for determination of body fat and adipose tissue biopsies. A new method of calculation of body fat in infants is presented. No sex differences were found. Body fat expressed as per cent of body weight increased from 16.2% to 28.1%. From 1 to 12 mo of age the expansion of body fat was explained by and increase in fat cell size, while in the age period 12-18 mo it was mainly due to an increase in fat cell number. At 18 mo lthe fat cell size was the same as in 8-yr-old girls and 22-yr-old women (normal-weight females previously studied). The fat cell number at 18 mo, however, was far below the number at 8 yr of age, as well as the still higher number of the 22-yr-old women.