Kevin J. Acheson

Effects of dietary fat on postprandial substrate oxidation and on carbohydrate and fat balances.

To study the effect of dietary fat on postprandial substrate utilization and nutrient balance, respiratory exchange was determined in seven young men for 1 h before and 9 h after the ingestion of one of three different breakfasts: i.e., bread, jam, and dried meat (482 kcal: 27% protein, 62% carbohydrate, and 11% fat); bread, jam, and dried meat plus 50 g of margarine containing long-chain triglycerides (LCT); or bread, jam, and dried meat plus 40 g medium-chain triglycerides (MCT) and 10 g LCT margarine (858 kcal: 15% protein, 35% carbohydrate, and 50% fat). Plasma glucose concentrations peaked 45 min after the start of the meals. When compared with the low fat meal, the LCT margarine supplement had no effect at any time on circulating glucose and insulin concentrations, nor on the respiratory quotient. When MCTs were consumed, plasma glucose and insulin concentrations remained lower and plasma FFA concentrations higher during the first 2 h. 9 h after the breakfasts, the amounts of substrates oxidized were similar in each case, i.e., approximately 320, 355, and 125 kcal for carbohydrate, fat, and protein, respectively. This resulted in comparable carbohydrate (mean +/- SD = -22 +/- 32, -22 +/- 37, and -24 +/- 22 kcal) and protein balances (-7 +/- 9, +7 +/- 7, and -8 +/- 11 kcal) after the low fat, LCT- and MCT-supplemented test meals, respectively. However, after the low fat meal, the lipid balance was negative (-287 +/- 60 kcal), which differed significantly (P less than 0.001) from the fat balances after the LCT- and MCT-supplemented meals, i.e., +60 +/- 33 and +57 +/- 25 kcal, respectively. The results demonstrate that the rates of fat and of carbohydrate oxidation are not influenced by the fat content of a meal.

Evidence that insulin resistance is responsible for the decreased thermic effect of glucose in human obesity.

The thermic effect of glucose was investigated in nine obese and six lean subjects in whom the same rate of glucose uptake was imposed. Continuous indirect calorimetry was performed for 240 min on the supine subject. After 45 min, 20% glucose was infused (609 mg/min) for 195 min and normoglycemia was maintained by adjusting the insulin infusion rate. At 2 h, propranolol was infused (bolus 100 micrograms/kg; 1 microgram/kg X min) for the remaining 75 min. To maintain the same glucose uptake (0.624 g/min), it was necessary to infuse insulin at 3.0 +/- 0.6 (leans) and 6.6 +/- 1.2 mU/kg X min (obese) (P less than 0.02). At this time, glucose oxidation was 0.248 +/- 0.019 (leans) and 0.253 +/- 0.022 g/min (obese) (NS), and nonoxidative glucose disposal was 0.375 +/- 0.011 and 0.372 +/- 0.029 g/min, respectively. Resting metabolic rate (RMR) rose significantly by 0.13 +/- 0.02 kcal/min in both groups, resulting in similar thermic effects, i.e., 5.5 +/- 0.7% (leans) 5.4 +/- 0.9% (obese) (NS) and energy costs of glucose storage 0.35 +/- 0.06 and 0.39 +/- 0.09 kcal/g (NS), respectively. With propranolol, glucose uptake and storage remained the same, while RMR fell significantly in both groups, with corresponding decreases (P less than 0.05) in the thermic effects of glucose to 3.7 +/- 0.6% and 2.9 +/- 0.8% (NS) and the energy costs of glucose storage 0.23 +/- 0.04 and 0.17 +/- 0.05 kcal/g (NS) in the lean and obese subjects, respectively. These results suggest that the defect in the thermic effect of glucose observed in obese subjects is due to their insulin resistance, which is responsible for a lower rate of glucose uptake and hence decreased rate of glucose storage, which is an energy-requiring process.

Effect of a Thermogenic Beverage on 24-Hour Energy Metabolism in Humans

Objective: To test whether consumption of a beverage containing active ingredients will increase 24‐hour energy metabolism in healthy, young, lean individuals.

Effect of carbohydrate overfeeding on whole body macronutrient metabolism and expression of lipogenic enzymes in adipose tissue of lean and overweight humans

OBJECTIVE: Lipids stored in adipose tissue can originate from dietary lipids or from de novo lipogenesis (DNL) from carbohydrates. Whether DNL is abnormal in adipose tissue of overweight individuals remains unknown. The present study was undertaken to assess the effect of carbohydrate overfeeding on glucose-induced whole body DNL and adipose tissue lipogenic gene expression in lean and overweight humans.DESIGN: Prospective, cross-over study.SUBJECTS AND METHODS: A total of 11 lean (five male, six female, mean BMI 21.0±0.5 kg/m2) and eight overweight (four males, four females, mean BMI 30.1±0.6 kg/m2) volunteers were studied on two occasions. On one occasion, they received an isoenergetic diet containing 50% carbohydrate for 4 days prior to testing; on the other, they received a hyperenergetic diet (175% energy requirements) containing 71% carbohydrates. After each period of 4 days of controlled diet, they were studied over 6 h after having received 3.25 g glucose/kg fat free mass. Whole body glucose oxidation and net DNL were monitored by means of indirect calorimetry. An adipose tissue biopsy was obtained at the end of this 6-h period and the levels of SREBP-1c, acetyl CoA carboxylase, and fatty acid synthase mRNA were measured by real-time PCR.RESULTS: After isocaloric feeding, whole body net DNL amounted to 35±9 mg/kg fat free mass/5 h in lean subiects and to 49±3 mg/kg fat free mass/5 h in overweight subjects over the 5 h following glucose ingestion. These figures increased (P<0.001) to 156±21 mg/kg fat free mass/5 h in lean and 64±11 mg/kg fat free mass/5 h (P<0.05 vs lean) in overweight subjects after carbohydrate overfeeding. Whole body DNL after overfeeding was lower (P<0.001) and glycogen synthesis was higher (P<0.001) in overweight than in normal subjects. Adipose tissue SREBP-1c mRNA increased by 25% in overweight and by 43% in lean subjects (P<0.05) after carbohydrate overfeeding, whereas fatty acid synthase mRNA increased by 66 and 84% (P<0.05).CONCLUSION: Whole body net DNL is not increased during carbohydrate overfeeding in overweight individuals. Stimulation of adipose lipogenic enzymes is also not higher in overweight subjects. Carbohydrate overfeeding does not stimulate whole body net DNL nor expression of lipogenic enzymes in adipose tissue to a larger extent in overweight than lean subjects.

Two-week stimulation or blockade of the sympathetic nervous system in man: Influence on body weight, body composition, and twenty four-hour energy expenditure

Seven lean healthy young men were studied for 6 weeks during exposure to pharmacologic inhibition or stimulation of the sympathetic nervous system. For a period of 2 weeks their beta-adrenergic receptors were either blocked with propranolol hydrochloride (160 mg/d) or stimulated with terbutaline sulphate (15 mg/d). After a further 2 weeks of placebo administration (500 mg lactose/d), the subjects crossed over to the drug they had not been taking at the beginning of the experiment for another 14 days. During the last five days of each 2-week period, the subjects consumed a weight-maintaining diet, composed of 12% protein, 48% carbohydrate, and 40% fat. They consumed exactly the same menus on the same days during the subsequent study periods. Body weight and physical activity were measured every day for 6 weeks. Daily heart rate and nitrogen excretion were measured continuously for days at the end of each 2-week period, the last two days of which were spent in a respiration chamber where energy expenditure and a variety of metabolic parameters were measured. In the respiration chamber on the propranolol, placebo, and terbutaline treatments, respectively, significant differences were observed in mean daily heart rate (65 +/- 3, 75 +/- 4, and 84 +/- 4 beats/min), mean sleeping heart rate (51 +/- 2, 56 +/- 3, and 62 +/- 3 beats/min), nitrogen excretion (13.6 +/- 0.7, 12.6 +/- 0.6, and 11.9 +/- 0.6 g/d), fat oxidation (+1,045 +/- 95, +1,243 +/- 148, and +1,278 +/- 84 kcal/d) and thyroid hormones (12.0 +/- 0.7, 15.7 +/- 0.9, and 17.2 +/- 1.0 T3/T4 ratio).(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of L-carnitine on submaximal exercise metabolism after depletion of muscle glycogen.

The effect of L-carnitine on energy metabolism at a high lipolytic flux was studied. Nine healthy male subjects received L-carnitine (CARN) (3 g.d-1) for 7 d, or a placebo (CONT), both with Ca pentothenate. The treatment increased resting nitrogen excretion slightly (+15%, P < 0.02). After an overnight fast, the subjects were submitted successively to 20 min bicycle exercise at 43 +/- 2 (SEM) %VO2max, a glycogen depletion routine involving high intensity bouts to exhaustion, 1-2 h of rest, again 20 min at the initial load, and finally 20 min at 57 +/- 3 %VO2max. After glycogen depletion, blood short-chain acylcarnitine concentrations increased 5 times as much in CARN as in CONT (P < 0.02). Fat oxidation estimated from respiratory gas exchange doubled after glycogen depletion for the same exercise intensity. However, there were no treatment differences in nonprotein RQ, heart rate, perceived fatigue, and blood parameters. It is concluded that during submaximal exercise after glycogen depletion (i.e., at a high lipid flux) substrate metabolism is not influenced by L-carnitine supplementation.

Carbohydrate for weight and metabolic control: where do we stand?

Changes in lifestyle are considered to play an important role in the etiology of obesity and type 2 diabetes, and improvements in diet and physical activity are the first-choice treatment for these metabolic diseases. Since the dietary recommendations of almost 40 y ago that fat should be decreased and that carbohydrate should be increased, recommendations for a healthy diet, except for minor amendments, have not changed that much. It is generally considered that caloric restriction is more important than changes in the macronutrient composition of the diet for weight loss and body weight control. Although this is true, there is increasing evidence that changes in the macronutrient composition of the diet (decreasing carbohydrate and increasing unsaturated fats and/or protein) play a role that facilitates weight loss, increases insulin sensitivity and glucose tolerance, and improves cardiovascular risk factors, such as blood pressure, blood lipid profile, and inflammatory markers, often independent of weight loss. Low-carbohydrate diets, whether they be high in unsaturated fats and/or protein, are not recommended by the American Diabetes Association; however, despite this the Joslin Diabetes Center currently advocates a diet composition of approximately 40% carbohydrate, 30% fat, and 30% protein energy for overweight and obese adults with type 2 diabetes or prediabetes or those at high risk of developing type 2 diabetes. Hopefully, future studies will indicate whether diets with a more equilibrated macronutrient composition than presently recommended are more appropriate for body weight and metabolic control.

The parasympathetic nervous system and the thermic effect of glucose/insulin infusions in humans

The thermic effect of glucose/insulin infusions was investigated in seven healthy young men before and during either inhibition (atropine sulphate 10 micrograms/kg bolus; 10 micrograms/kg/h) or stimulation (edrophonium chloride, 10 mg bolus; 0.75 mg/min starting rate) of the parasympathetic nervous system. The thermic effects of glucose/insulin were 6.2% +/- 0.4% and 5.6% +/- 0.7% before atropine and edrophonium, respectively, and increased to 7.1% +/- 0.5% (NS) with atropine and 7.5% +/- 1.2% (P less than .05) with edrophonium. In four subjects atropine or edrophonium was infused before the hyperinsulinemic, euglycemic clamp. A significant increase in resting metabolic rate and plasma norepinephrine concentrations was observed with edrophonium alone. When the thermic effects of glucose/insulin were calculated with respect to the metabolic rates observed during the drug infusions alone, they were 5.9% +/- 1.4% and 3.6% +/- 0.6% (NS) for the clamp + atropine and clamp + edrophonium, respectively. These results demonstrate that the increases in the thermic effect of glucose/insulin infusions observed during inhibition or stimulation of the parasympathetic nervous system were due to atropine or edrophonium increasing the resting metabolic rate rather than increasing the thermic response to glucose-insulin infusions. However, because it has been shown that atropine can decrease the thermic effect of an orally administered meal by approximately 60%, it would appear that the parasympathetic nervous system can influence the thermic effect of food by affecting the rate of digestion, absorption and storage of the ingested nutrients.

Thyroid hormone action on lipid metabolism in humans: A role for endogenous insulin

The effects of moderate hyperthyroidism on lipid metabolism were investigated in six healthy subjects before and after thyroxine treatment (300 micrograms/d). T4-treatment increased basal metabolic rate (+8%) and glucose oxidation (+87%), without affecting lipid oxidation, plasma free fatty acids, glycerol, and beta-hydroxybutyrate. During euthyroidism, a hypoinsulinaemic-euglycaemic 150-minute clamp protocol increased energy expenditure (+3%), lipid oxidation (+42%), plasma free fatty acids (+254%), glycerol (+232%), and beta-hydroxybutyrate (+343%), but decreased glucose oxidation (-20%). Similar effects were observed after T4-treatment, but hyperthyroidism induced disproportionate increases in energy expenditure (+7%), plasma glycerol (+310%), and ketone body levels (+436%). We conclude that moderate hyperthyroidism enhances hypoinsulinemia-induced increases in lipolysis, free fatty acid recycling, and ketogenesis without affecting lipid oxidation. Thus basal insulin may camouflage some of thyroid hormone action on lipid metabolism.

Effects of glucose and amino acid infusion on glucose turnover in insulin-resistant obese and type II diabetic patients

Glucose turnover was assessed from [6,6-2H]glucose and [U-13C]glucose dilution analysis in six lean nondiabetic subjects, six obese patients with normal glucose tolerance, and six obese patients with non-insulin-dependent diabetes mellitus (NIDDM) during sequential infusions of glucose (13.9 mumol/kg fat-free mass [FFM]/min) and glucose+amino acid (4.2 mg/kg FFM/min). Cori cycle activity was assessed from the difference between glucose turnover obtained from [6,6-2H]glucose and [U-13C]glucose. During infusion of glucose alone, total glucose turnover was increased by 70% in obese NIDDM patients. Amino acid infusion decreased glucose concentrations by 0.8, 0.5, and 1.8 mmol/L in controls, obese patients, and NIDDM patients, respectively. This decrease in glycemia occurred despite an increase in glucose turnover in lean and obese nondiabetic subjects, and was due to an increased metabolic clearance rate (MCR) of glucose. In NIDDM patients the MCR of glucose was unchanged, and the decrease in glycemia was explained by a diminution in hepatic glucose output. Glucose turnover obtained by [6.6-2H] dilution analysis exceeded significantly the values obtained by dilution analysis in obese subjects and obese NIDDM patients, but not in controls. This indicates an increased Cori cycle activity in these patients.