Adipose tissue fatty acid storage factors: effects of depot, sex and fat cell size.

BACKGROUND/OBJECTIVES: Patterns of postabsorptive adipose tissue fatty acid storage correlate with sex-specific body fat distribution. Some proteins and enzymes participating in this pathway include CD36 (facilitated transport), acyl-CoA synthetase (ACS; the first step in fat metabolism) and diacylglycerol acetyltransferase (DGAT; the final step of triglyceride synthesis). Our aim was to better define CD36, ACS and DGAT in relation to sex, subcutaneous fat depots and adipocyte size. SUBJECTS/METHODS: Data were collected from studies conducted at Mayo Clinic between 2004 and 2012. Abdominal and femoral subcutaneous fat biopsy samples must have been collected in the postabsorptive state from healthy males and premenopausal females. Body composition was measured with dual-energy X-ray absorptiometry and abdominal computerized tomography scans. Adipocyte size (microscopy), CD36 protein content (enzyme-linked immunosorbent assay) and ACS and DGAT enzyme activities were measured. Data are presented as medians and 25th, 75th quartiles. RESULTS: Males (n=60) and females (n=78) did not differ by age (37; 28, 46 years), body mass index (28.4; 24.6, 32.1 kg m(-)(2)) or abdominal (0.60; 0.45, 0.83 µg lipid per cell) and femoral adipocyte size (0.76; 0.60, 0.94 µg lipid per cell). Femoral ACS and DGAT were greater in females than males when expressed per mg lipid (ACS: 73 vs. 55 pmol/mg lipid/min; DGAT: 5.5 vs. 4.0 pmol/mg lipid/min; P<0.0001 for both) and per 1000 adipocytes (ACS: 59 vs. 39 pmol per min per 1000 adipocytes; DGAT: 4.3 vs 3.1 pmol per min per 1000 adipocytes; P⩽0.0003 for both). There were no differences in abdominal fat storage factors between sexes. ACS and DGAT decreased as a function of adipocyte size (P<0.0001 for both). The decrease in ACS was greater in males and abdominal subcutaneous fat. There were no sex differences in CD36 in either fat depot, nor did it vary across adipocyte size. CONCLUSIONS: Facilitated transport of fatty acids by CD36 under postabsorptive conditions would not be different in those with large vs small adipocytes in either depot of both sexes. However, intracellular trafficking of fatty acids to triglyceride storage by ACS and DGAT may be less efficient in larger adipocytes.

Erythrocyte fatty acid composition and insulin sensitivity in daughters of Type 2 diabetic patients and women with no family history of diabetes.

BACKGROUND: There is evidence that the impact of environmental factors on insulin sensitivity is modified by the presence of family history of diabetes. AIM: To compare the association between the erythrocyte phospholipid fatty acid composition (a biomarker of dietary fatty acids) and insulin sensitivity in daughters of Type 2 diabetic patients with the corresponding association in women without family history of diabetes. MATERIAL/SUBJECTS AND METHODS: Eighteen offspring of Type 2 diabetic patients [age 30+/-6.5 yr; body mass index (BMI) 22.2+/-2.5 kg/m2; body fat 31.8+/-5.1%] and 18 matched women (age 30.1+/-6.8 yr; BMI 22.2+/-1.8 kg/m2; body fat 32.2+/-6.0%) participated in the study. RESULTS: Insulin Sensitivity Index (ISI)-Matsuda tended to be lower (p=0.06) in the Offspring than the control group. Weight proportions of erythrocyte phospholipid saturated (SFA), polyunsaturated (PUFA), and monounsaturated fatty acids (MUFA) were similar between the two groups. In the offspring, erythrocyte total SFA were negatively correlated with ISI-Matsuda [r=-0.47, p<0.05), ISI(gly)-Belfiore (r=-0.52, p<0.05) and ISI(ffa)-Belfiore (r=-0.53, p<0.05)], whereas total PUFA were positively correlated with insulin sensitivity [ISI-Matsuda, r=0.46, p<0.05; ISI(gly)-Belfiore, r=0.53, p<0.05; ISI(ffa)-Belfiore, r=0.54, p<0.05]. No significant correlations were observed in the control group. CONCLUSIONS: The associations between erythrocyte fatty acid composition and insulin sensitivity are distinct between daughters of Type 2 diabetic patients and women without family history of diabetes.

Plasma NEFA storage in adipose tissue in the postprandial state: sex-related and regional differences.

AIMS/HYPOTHESIS: We recently reported that a small fraction of circulating NEFA is stored through direct uptake in subcutaneous fat in postabsorptive humans in vivo and that this pathway may favour lower-body fat distribution in women. Here, we examined sex-related and regional differences in storage of plasma NEFA in subcutaneous adipose tissue during postprandial conditions. METHODS: At 1 h after lunch, men and women of normal weight received an intravenous bolus of approximately 1.66 MBq [1-(14)C]oleate followed by timed subcutaneous fat biopsies. The preceding breakfast was either a normal- or high-fat meal; the high-fat breakfast was used to create postprandial oleate concentrations in the postabsorptive range. RESULTS: Storage of the NEFA tracer in adipose tissue (dpm/g lipid) was greater in women; in both sexes abdominal fat stored tracer more avidly than femoral fat. A greater fraction of the administered tracer was stored in whole body subcutaneous fat of women than in that of men (27 +/- 3 vs 8 +/- 1%, respectively, p < 0.0001). No significant differences in tracer storage were observed between participants consuming the high- vs normal-fat breakfast. CONCLUSIONS/INTERPRETATION: Postprandial NEFA storage in subcutaneous fat through direct uptake accounts for approximately 25% of NEFA disposal in women, but for <10% in men in a wide range of circulating NEFA concentrations. It is greater in the upper- than lower-body subcutaneous fat, favouring upper-body fat accumulation in both sexes.

Committed subcutaneous preadipocytes are reduced in human obesity.

AIMS/HYPOTHESIS: The aim of this study was to test whether the availability of committed preadipocytes in abdominal and femoral subcutaneous adipose tissue varies with obesity and body fat distribution. METHODS: Body composition, fat cell size, committed preadipocytes and macrophages were measured in subcutaneous abdominal and femoral adipose depots of 17 lean, 16 upper-body-obese (UBO) and 13 lower-body-obese (LBO) women. Preadipocytes and macrophages were identified by simultaneous staining with the respective markers aP2 and CD68. In a subset of samples we measured preadipocyte proliferation, differentiation and susceptibility to apoptosis. RESULTS: Abdominal adipocytes were smaller in lean than in obese women. Committed preadipocytes represented a greater fraction of stromovascular cells in lean than in obese women but were similar between UBO and LBO women (abdomen: approximately 30 +/- 3 vs approximately 17 +/- 2%; thigh: approximately 30 +/- 3 vs approximately 17 +/- 2%). Preliminary data suggested that preadipocyte kinetics were similar in LBO and lean women, whereas preadipocytes of UBO women differentiated less and were more susceptible to apoptotic stimuli. The fraction of stromovascular cells that were macrophages was greater in both depots in obese women (UBO and LBO) than in normal-weight women, but the difference was not statistically significant. CONCLUSIONS/INTERPRETATION: The proportion of subcutaneous adipose tissue stromovascular cells that are committed preadipocytes is reduced with obesity. This could be due to greater recruitment of preadipocytes to adipogenesis or greater preadipocyte apoptosis, depending upon the obesity phenotype. These data are consistent with the concept that body fat distribution may be regulated partly through differences in adipogenesis.

Gender influence on plasma triacylglycerol response to meals with different monounsaturated and saturated fatty acid content.

OBJECTIVE: Both gender and meal fatty acid composition modulate postprandial triacylglycerol (TAG) metabolism, but little information exists on their interaction. We compared postprandial TAG concentrations in men and women after test meals differing in the proportion of monounsaturated (MUFA) and saturated fatty acids (SFA). SUBJECTS: Nine men (body mass index, BMI: 24.5+/-2.3 kg/m(2)) (mean+/-s.d.) and 10 premenopausal women (BMI: 21.2+/-1.7 kg/m(2)), young and healthy, habituated to a relatively high MUFA diet. DESIGN: Plasma responses were studied after subjects consumed two meals, each providing 60 g of fat and 4.7 MJ, on different occasions: one meal was rich in MUFA (MUFA meal: 40 g MUFA; 12 g SFA) and the other meal was rich in SFA (SFA meal: 20 g MUFA; 32 g SFA). The total body and abdominal fat mass were assessed by dual energy X-ray absorptiometry. RESULTS: Fasting plasma TAG concentration did not differ between meals or genders. No gender differences were observed in either total body or abdominal fat mass. The area under the plasma concentration vs time curve was on average 60% higher (P<0.001) in men than women. Repeated measures ANOVA showed a significant effect of meal x time interaction in men (P<0.001) but not in women (P=0.84). In men, maximal plasma TAG occurred at 4 h and was significantly greater after the MUFA meal (2.10+/-0.20 mmol/l) (mean+/-s.e.m.) than after the SFA meal (1.66+/-0.19 mmol/l) (P=0.01). TAG concentration at 5 h was also significantly greater after the MUFA meal. In women, the patterns of TAG responses were identical after the MUFA and SFA meals. CONCLUSIONS: This study provides evidence that gender influences postprandial TAG concentrations when meal fatty acid composition is altered.

Plasma leptin is influenced by diet composition and exercise.

OBJECTIVE: A low-fat, high-carbohydrate diet (

Exercise prevents the accumulation of triglyceride-rich lipoproteins and their remnants seen when changing to a high-carbohydrate diet.

We tested the hypothesis that daily aerobic exercise opposes the fasting hypertriglyceridemia and exaggerated postprandial lipemia observed after substituting dietary fat with carbohydrate. Eight healthy postmenopausal women aged 51 to 66 years consumed the same high-fat mixed meal on 3 occasions: (1) after 3 days on a low-carbohydrate diet (35%, 50%, and 15% energy from carbohydrate, fat, and protein, respectively); (2) after 3 days on an isoenergetic high-carbohydrate diet (corresponding values 70%, 15%, and 15%); and (3) after 3 days on the same high-carbohydrate diet with 60 minutes of brisk walking daily. Plasma triglycerides were higher after the high-carbohydrate diet than after the low-carbohydrate diet: fasting, 1.58+/-0.19 versus 0.96+/-0.12 mmol/L, respectively; 6-hour postprandial area under concentration versus time curve, 13.74+/-1.57 versus 10.12+/-1.15 (mmol/L)xhour, respectively (both P<0.01). In the fasted and postprandial states, concentrations of apolipoproteins B-48 and B-100 in the triglyceride-rich lipoprotein fraction were significantly higher after the high-carbohydrate diet, as was the concentration of remnant-like lipoprotein particle cholesterol (a measure of lipoprotein remnants). These carbohydrate-induced increases in the number of circulating triglyceride-rich particles and their remnants were abolished when subjects had exercised daily during the high-carbohydrate diet.

Exercise prevents the augmentation of postprandial lipaemia attributable to a low-fat high-carbohydrate diet.

There is concern that replacement of dietary fat with carbohydrate may not reduce the overall risk of CHD because this replacement strategy elevates postprandial plasma triacylglycerol (TAG) concentrations. The present study was designed to test the hypothesis that daily exercise can offset the augmented postprandial lipaemia associated with a short-term high-carbohydrate diet. Nine healthy, normolipidaemic men aged 33 (sd 4) years consumed a test meal (g/kg body mass; 1.2 fat, 1.1 carbohydrate, 0.2 protein) on three occasions: after 3 d on a typical Western diet (46, 38 and 16 % energy from carbohydrate, fat and protein respectively); after 3 d on an isoenergetic high-carbohydrate diet (corresponding values: 70, 15 and 15 % energy); after 3 d on the same high-carbohydrate diet with 30 min moderate exercise daily. Fasting plasma TAG concentration was higher after the high-carbohydrate diet (1.15 (se 0.16) mmol/l) than after the Western diet (0.83 (se 0.10) mmol/l; ). Similarly, postprandial lipaemia (6 h total area under plasma TAG concentration v. time curve) was higher after the high-carbohydrate diet (12.54 (se 2.07) mmol/l.h) than after the Western diet (9.30 (se 1.30) mmol/l.h; ). The addition of exercise to the high-carbohydrate diet significantly reduced postprandial lipaemia (9.95 (se 1.94) mmol/l.h; when compared with the high-carbohydrate diet) but not fasting TAG concentration (1.02 (se 0.24) mmol/l). In conclusion, daily exercise prevented the augmentation of postprandial lipaemia attributable to the short-term high-carbohydrate diet and, thus, exercise may be a powerful adjunct to dietary change.

Postprandial lipemia after short-term variation in dietary fat and carbohydrate.

Replacement of dietary fat with carbohydrate may not reduce the overall risk of coronary heart disease (CHD), because this elevates plasma triacylglycerol (TAG) concentrations. The lipoproteinemic effects of a high-carbohydrate diet are likely to be more marked shortly after the initiation of such a diet than after longer periods of intervention during which adaptive processes may counteract the initial effects. Therefore, we studied the postprandial responses to a standard meal after 3-day dietary intervention periods. An additional objective was to establish a model for future study of the mechanisms involved. Nine normolipidemic men consumed the meal (1.2 g fat, 1.1 g carbohydrate, and 0.2 g protein per 1 kg body mass) after 3 days on a high-carbohydrate diet (68% +/- 3% energy from carbohydrate, mean +/- SD) and also after 3 days on an isoenergetic high-fat diet (66% +/- 5% energy). Venous blood samples were obtained from fasted subjects and for 6 hours after the meal. In the fasted state, TAG was higher after the high-carbohydrate diet (1.18 +/- 0.18 v0.62 +/- 0.09 mmol/L, mean +/- SEM, P = .02) and high-density lipoprotein (HDL) cholesterol was lower (1.01 +/- 0.08 v 1.10 +/- 0.09 mmol/L, P = .002). The area under the plasma TAG concentration versus time curve was 42% +/- 7% higher after the high-carbohydrate diet (P = .003). After the high-carbohydrate diet, the postprandial insulin response did not differ between trials, but glucose and 3-hydroxybutyrate responses were lower (P = .009 and P = .02, respectively) and the lactate response was higher (P = .001). Plasma nonesterified fatty acids (NEFAs) were lower after the high-carbohydrate diet in the fasted state and for 4 hours postprandially, but were higher thereafter (interaction of time x trial, P = .001). These results indicate that compared with a high-fat diet, the plasma TAG response to a standard high-fat meal is markedly higher after a few days on a high-carbohydrate diet, with major differences in the associated metabolic milieu. The magnitude of these changes and the rapidity with which they developed suggest that this model may be attractive for future studies of the underlying mechanisms.

Exercise-induced changes in the concentration of individual fatty acids and triacylglycerols of human plasma.

Nineteen male handball players played for two 30-minute periods with a 10-minute interval. Blood samples were drawn at rest, at halftime, and at the end of the game. A biopsy of subcutaneous fat was also taken from 14 participants. Mean plasma lactate concentration was not greater than 4 mmol/L at the end of either half. The concentration of nonesterified fatty acids (NEFA) in plasma increased gradually but not uniformly throughout the game. In effect, the percentages of the major NEFA were significantly different at the three time points of sampling: palmitate (16:0) and stearate (18:0) decreased and oleate (18:1) and linoleate (18:2) increased, resulting in an increase of the ratio of unsaturated to saturated fatty acids (U/S) from 1.1 at rest to 1.6 at the end. The concentration of plasma triacylglycerols (TG) declined during the game, but nine of 19 subjects showed increases during one or both halves, implying a stimulation of TG release from the liver during exercise, which can, at times, overcome the increased hydrolysis of TG in muscle capillaries. Changes in the acyl-group distribution of plasma TG were minor but also in favor of unsaturated fatty acids. Changes in NEFA composition tended toward the composition of adipose tissue, in which TG had a U/S ratio of 3.2. Linear regression between changes in the total concentration of plasma NEFA during each half of the game and corresponding changes in the concentration of individual NEFA showed that the contributions (slopes) of myristate (14:0), palmitoleate (16:1), 18:0, and 18:2 were not significantly different from their fractions in adipose tissue TG.(ABSTRACT TRUNCATED AT 250 WORDS)