Mo L. Clark

Substituting dietary saturated fat with polyunsaturated fat changes abdominal fat distribution and improves insulin sensitivity.

Abstract.Aims/hypothesis: British dietary recommendations are to decrease total fat intake to less than 30 % of daily energy intake and saturated fat to less than 10 %. In practice, it is difficult for people to make these changes. It may be easier to encourage people to switch from a diet rich in saturated fatty acids to one rich in polyunsaturated fatty acids. Methods: A total of 17 subjects – six people with Type II (non-insulin-dependent) diabetes mellitus, six non-obese and five obese people without diabetes – were randomised to spend two 5-week periods on a diet rich in saturated or in polyunsaturated fatty acids, in a crossover design. At the start of the study and after each dietary period, we assessed abdominal fat distribution using magnetic resonance imaging, insulin sensitivity using hyperinsulinaemic-euglycaemic clamps and fasting lipid parameters. Results: Dietary compliance, assessed by weekly 3-day dietary records and measurement of biochemical markers, was good. Energy and fat intake appeared to be reduced on the diet rich in polyunsaturated fatty acids although body weights did not change. Insulin sensitivity and plasma low density lipoprotein cholesterol concentrations improved with the diet rich in polyunsaturated fatty acids compared with the diet rich in saturated fatty acids. There was also a decrease in abdominal subcutaneous fat area. Conclusion/interpretation: If this result is confirmed in longer-term studies, this dietary manipulation would be more readily achieved by the general population than the current recommendations and could result in considerable improvement in insulin sensitivity, reducing the risk of developing Type II diabetes. [Diabetologia (2002) 45: 369–377]

Effects of an oral and intravenous fat load on adipose tissue and forearm lipid metabolism

We have studied the fate of lipoprotein lipase (LPL)-derived fatty acids by measuring arteriovenous differences across subcutaneous adipose tissue and skeletal muscle in vivo. Six subjects were fasted overnight and were then given 40 g of triacylglycerol either orally or as an intravenous infusion over 4 h. Intracellular lipolysis (hormone-sensitive lipase action; HSL) was suppressed after both oral and intravenous fat loads ( P < 0.001). Insulin, a major regulator of HSL activity, showed little change after either oral or intravenous fat load, suggesting that suppression of HSL action occurred independently of insulin. The rate of action of LPL (measured as triacylglycerol extraction) increased with both oral and intravenous fat loads in adipose tissue ( P = 0.002) and skeletal muscle ( P = 0.001). There was increased escape of LPL-derived fatty acids into the circulation from adipose tissue, shown by lack of reesterification of fatty acids. There was no release into the circulation of LPL-derived fatty acids from skeletal muscle. These results suggest that insulin is not essential for HSL suppression or increased triacylglycerol clearance but is important in reesterification of fatty acids in adipose tissue but not uptake by skeletal muscle, thus affecting fatty acid partitioning between adipose tissue and the circulation, postprandial nonesterified fatty acid concentrations, and hepatic very low density lipoprotein secretion.We have studied the fate of lipoprotein lipase (LPL)-derived fatty acids by measuring arteriovenous differences across subcutaneous adipose tissue and skeletal muscle in vivo. Six subjects were fasted overnight and were then given 40 g of triacylglycerol either orally or as an intravenous infusion over 4 h. Intracellular lipolysis (hormone-sensitive lipase action; HSL) was suppressed after both oral and intravenous fat loads (P < 0.001). Insulin, a major regulator of HSL activity, showed little change after either oral or intravenous fat load, suggesting that suppression of HSL action occurred independently of insulin. The rate of action of LPL (measured as triacylglycerol extraction) increased with both oral and intravenous fat loads in adipose tissue (P = 0.002) and skeletal muscle (P = 0.001). There was increased escape of LPL-derived fatty acids into the circulation from adipose tissue, shown by lack of reesterification of fatty acids. There was no release into the circulation of LPL-derived fatty acids from skeletal muscle. These results suggest that insulin is not essential for HSL suppression or increased triacylglycerol clearance but is important in reesterification of fatty acids in adipose tissue but not uptake by skeletal muscle, thus affecting fatty acid partitioning between adipose tissue and the circulation, postprandial nonesterified fatty acid concentrations, and hepatic very low density lipoprotein secretion.

Acute effect of fructose on postprandial lipaemia in diabetic and non-diabetic subjects

We investigated whether the potentiation of postprandial lipaemia by fructose occurs in both non-diabetic subjects and those with non-insulin-dependent diabetes mellitus. Six non-diabetic and six diabetic subjects were studied on two occasions. They were given a meal containing 1 g fat/kg body weight with, on one occasion, 0.75 g fructose/kg body weight, on the other occasion 0.75 g starch/kg body weight. In both groups, plasma glucose and insulin concentrations rose more after starch than after fructose. At 1-2 h after the meal, plasma non-esterified fatty acid concentrations were suppressed more after fructose than after starch, but later they rose more after fructose than after starch. Plasma triacylglycerol concentrations rose more slowly after fructose, but were considerably higher than those after starch from 4-6 h after the meal. There were no differences in post-heparin plasma lipoprotein lipase (EC 3.1.1.34) activity at the end of the test. The potentiation of postprandial lipaemia by fructose was positively related to the fasting plasma insulin concentration, suggesting that insulin-resistant subjects are more prone to this effect. We conclude that the potentiation of postprandial lipaemia by fructose is seen in both diabetic and non-diabetic subjects. Our results suggest that alterations in the dynamics of plasma non-esterified fatty acids might underlie the effects of fructose on triacylglycerol metabolism.

Adipose tissue metabolism in the postprandial period: microdialysis and arteriovenous techniques compared.

We investigated whether two different methods of studying metabolism in adipose tissue, microdialysis and the arteriovenous technique, produced comparable results during the postprandial period. Interstitial glycerol concentrations measured by microdialysis are usually used as an index of intracellular lipolysis, and it is not known whether they also reflect the intravascular action of lipoprotein lipase in the postprandial period. The two techniques were compared in 10 healthy subjects fed mixed meals. Interstitial glycerol concentrations reflected those measured in adipose tissue venous plasma. However, the calculation of the rate of glycerol release from adipose tissue using the microdialysis data differed systematically from that using arteriovenous difference measurement. The former method gave, on average, 40% lower values than the latter one. The difference is probably due to the assumptions that had to be made for the calculation of glycerol release. The two techniques have complementary places in the study of postprandial adipose tissue metabolism, with microdialysis reflecting intracellular hormone-sensitive lipase action rather than intravascular lipoprotein lipase.We investigated whether two different methods of studying metabolism in adipose tissue, microdialysis and the arteriovenous technique, produced comparable results during the postprandial period. Interstitial glycerol concentrations measured by microdialysis are usually used as an index of intracellular lipolysis, and it is not known whether they also reflect the intravascular action of lipoprotein lipase in the postprandial period. The two techniques were compared in 10 healthy subjects fed mixed meals. Interstitial glycerol concentrations reflected those measured in adipose tissue venous plasma. However, the calculation of the rate of glycerol release from adipose tissue using the microdialysis data differed systematically from that using arteriovenous difference measurement. The former method gave, on average, 40% lower values than the latter one. The difference is probably due to the assumptions that had to be made for the calculation of glycerol release. The two techniques have complementary places in the study of postprandial adipose tissue metabolism, with microdialysis reflecting intracellular hormone-sensitive lipase action rather than intravascular lipoprotein lipase.

Periprandial regulation of lipid metabolism in insulin-treated diabetes mellitus.

We have examined the regulation of lipid and glucose metabolism in the postabsorptive and postprandial states in six subjects with insulin-treated diabetes mellitus, and compared them with eight nondiabetic subjects. Blood or plasma concentrations of metabolites and fluxes across forearm and subcutaneous adipose tissue were studied after an overnight fast and for 6 hours after a mixed meal (3.1 MJ, 41% from fat). In the postabsorptive state, regulation of lipid metabolism in the two groups appeared basically similar except that a wider spread of plasma (free) insulin concentrations in the diabetic group led to a wider range of values of plasma nonesterified fatty acid (NEFA) release from adipose tissue, plasma NEFA concentrations, and blood ketone body concentrations. Extraction of ketone bodies across adipose tissue was positively correlated with arterial concentration in both groups (as it was in the forearm), confirming the ability of human adipose tissue to utilize ketone bodies. A single subcutaneous injection of insulin before the meal in the diabetic group produced a plasma free-insulin profile that was blunted and prolonged compared with the postprandial response in the control group. Postprandial forearm glucose uptake followed very closely the plasma (free) insulin concentration. Postprandial suppression of NEFA release from adipose tissue was essentially normal in the diabetic group, and the normal postprandial decrease in plasma NEFA concentrations was reproduced extremely closely. Forearm and adipose tissue blood flow did not differ between the groups.(ABSTRACT TRUNCATED AT 250 WORDS)