Jacques Delarue

Anthropometric values in an elderly French population

We compared anthropometric indices in samples of elderly people aged 65 years and over living in two French areas. The samples were divided into four age-groups (65-69, 70-74, 75-79 and over 80 years). We observed interregional differences in women aged 65-69 years and in men aged 65-74 years. Weight and anthropometric variables related to body fat percentage and to muscle mass showed a decline with age as already reported by others. We established anthropometric percentile values according to sex in pooled subjects when no integrated difference was found. The 50th percentile of arm circumference, muscle arm circumference and triceps skinfold was higher, and the 50th percentile of body mass index was lower than the one reported for the same indices from an elderly Welsh population. Our results show that an interregional difference in anthropometric indices exists in the elderly. The differences which are observed between our results and those reported from a British population emphasize the importance of establishing local values for the elderly population.

Mechanisms and kinetics of alpha-linolenic acid uptake in Caco-2 clone TC7

The uptake kinetics of alpha-linolenic acid (18:3(n - 3)), an essential fatty acid, were investigated in the human intestinal cell line Caco-2. Four clones (PD10, PF11, PD7 and TC7) from the heterogeneous parental Caco-2 cells population were used. After a screening step using isolated cells, the TC7 clone was selected for the study of alpha-linolenic acid uptake. [1-(14)C]linolenic acid dissolved in 10 mM taurocholate was presented to the microvillus plasma membrane (apical side) of TC7 differentiated cells, grown on a semi-permeable polycarbonate membrane. The results show that the initial rate of uptake is not a linear function of the 18:3(n- 3) monomer concentration in the incubation medium. In the monomer concentration range studied (0.2 to 36 microM) apical uptake was saturable and followed Michaelis-Menten kinetics (V(max) = 15.4 +/- 0.6 nmol/mg protein per min, K(m) = 14.3 +/- 1.3 microM). In addition, it was temperature- and energy-dependent but was apparently unaffected by the sodium gradient and intracellular metabolic fate of 18:3(n - 3). Excess of unlabeled saturated or unsaturated long chain fatty acids (C16 to C22) led to a 27-68% reduction of [1-(14)C]linolenic acid uptake. Likewise basolateral uptake was saturable (V(max) = 4.9 +/- 0.7 nmol/mg protein per min, K(m) = 8.7 +/- 2.9 microM). These facts argue in favour of the existence in these human intestinal cells of a carrier-mediated transport system for alpha-linolenic acid and probably other long chain fatty acids as well.

Fish-oil supplementation reduces stimulation of plasma glucose fluxes during exercise in untrained males.

The present study examined the effects of a 3-week fish-oil supplementation (6 g/d) on the rate of plasma glucose disappearance (Rd glucose), hepatic glucose production (HGP), carbohydrate oxidation and lipid oxidation during exercise. Six untrained males (23+/-1 years; 67.6+/-2.7 kg) performed two 90 min cycling exercise sessions at 60 % of maximal O2 output separated by 20 d. During the 20 d before the first test, they ingested 6 g olive oil/d, then 6 g fish oil/d during the 20 d before the second test. Plasma glucose fluxes and lipolysis were traced using 6,6-[(2)H2]glucose and 1,1,2,3,3-[(2)H5]glycerol respectively. Substrates oxidation was obtained from indirect calorimetry. At rest HGP and the Rd glucose were similar after olive oil and fish oil (1.83 (SE 0.05) v. 1.67 (SE 0.11) mg/kg per min). During exercise, fish oil reduced the stimulation of both the Rd glucose (5.06 (SE 0.23) v. 6.37 (SE 0.12) mg/kg per min; P<0.05) and HGP (4.88 (SE 0.24) v. 5.91 (SE 0.21) mg/kg per min; P<0.05). Fish oil also reduced glucose metabolic clearance rate (6.93 (SE 0.29) v. 8.30 (SE 0.57) ml/min). Carbohydrate oxidation tended to be less stimulated by exercise after fish oil than after olive oil (12.09 (SE 0.60) v. 13.86 (se 1.11) mg/kg per min; NS). Lipid oxidation tended to be more stimulated by exercise after fish oil (7.34 (SE 0.45) v. 6.85 (SE 0.17) mg/kg per min; NS). Glycaemia, lactataemia, insulinaemia and glucagonaemia were similarly affected by exercise after fish oil and olive oil. Lipolysis at rest was similar after fish oil and olive oil (2.92 (SE 0.42) v. 2.94 (SE 0.28) micromol/kg per min) and similarly stimulated by exercise (6.42 (SE 0.75) v. 6.77 (SE 0.72) micromol/kg per min). It is concluded that fish oil reduced the Rd glucose by 26 % by reducing glucose metabolic clearance rate, possibly by facilitating fat oxidation, and reduced HGP by 21%, possibly by a feedback mechanism.

Age-related insulin resistance: a review.

Impaired glucose tolerance occurs with age. This impairment is multifactorial including a decrease in insulin-mediated glucose uptake by peripheral tissues and a delay in insulin-induced suppression of hepatic glucose output. A post-binding defect in insulin action such as a reduced capacity to transcribe more glucose transporter mRNA and/or a reduced translocation of preformed glucose transporters to plasma membrane is incriminated. However, insulin resistance with age is not a constant finding and other mechanism(s) has (have) to be involved in old individuals with impaired glucose tolerance and normal tissue insulin sensitivity.

Change in energy and protein status during chemotherapy in patients with acute leukemia

The energy and protein status of 12 adult patients with acute leukemia (AL) was investigated during induction chemotherapy. Parenteral nutrition (PN) (nonprotein [NP], 31.4 kcal/kg/d; nitrogen [N], 0.177 g/kg/d) was started on day 6 after the beginning of chemotherapy and continued through all of the cytopenic phase. A clinical and metabolic evaluation, including measurement of resting energy expenditure (REE) by indirect calorimetry, was performed on each patient within the 2 days before beginning chemotherapy (D0), on the third day of chemotherapy (D3), and then weekly from day 7 until the end of the cytopenic phase. Measured REE at day 0 (29.5 ± 1.4 kcal/kg/d) was significantly higher (+34 ± 6%) than theoretical REE. Chemotherapy induced a significant decrease in REE at day 3 (26.2 ± 1.7 kcal/kg/d; P < 0.05), but during the cytopenic phase REE was not different significantly from its initial values (D0). A positive energy balance was observed during the whole study after the beginning of PN. In contrast, mean nitrogen balance remained negative always, due to a sharp increase in urinary nitrogen loss during the cytopenic phase. The fact that nutritional support falls short of its goal may explain why no improvement in tumor response to therapy has been described in most studies.

Effect of chemotherapy on resting energy expenditure in patients with non-Hodgkin's lymphoma. Results of a sequential study.

This study compared the resting energy expenditure (REE) modifications observed during successive intensive identical chemotherapy courses in non‐Hodgkins lymphoma patients to assess indirectly the metabolic changes induced by the cytotoxic effect of drugs on the tumor. With this therapeutic regimen, reduction of tumor mass is mostly achieved during the first course of chemotherapy. The study included 10 non‐Hodgkins lymphoma adult patients receiving three intensive 5‐day courses of Adriamycin (doxorubicin Adria Laboratories, Columbus, OH), cyclophosphamide, vindesine, and bleomycin. Resting energy expenditure was evaluated by indirect calorimetry during each course, first within the first 2 days before chemotherapy and then on days 2, 3 and 5. Initial REE (day 0) on entry into the study (21.8 ± 1.2 kcal/kg.d−1) represented 99 ± 6.7% of theoretical REE. Resting energy expenditure on day 0 was lower during course 2 and 3 (19.1 ± 0.7 and 18.4 ± 1.8 kcal/kg/d) than during course 1 (21.8 ± 1.2 kcal/kg/d). The REE profile was different among the 3 courses: course 1 induced a significant REE decrease on days 3 and 5 (P < 0.01); during course 2, REE remained stable and was lower than during course 1; during course 3, REE increased on days 2, 3, and 5 (P < 0.05). Energy balance was positive during the three courses and nutritional status remained stable. The REE decrease observed during course 1 may be regarded as the metabolic effect of chemotherapy on the tumor metabolism.

Nonalcoholic fatty liver disease: Roles of the gut and the liver and metabolic modulation by some dietary factors and especially long‐chain n‐3 PUFA

Nonalcoholic fatty liver disease (NAFLD), including nonalcoholic steatohepatitis (NASH), is the leading cause of chronic liver disease in Western countries. NASH increases the risk for fibrosis, cirrhosis, and hepatocellular carcinoma. The mechanisms underlying the steatosis to NASH transition remain incompletely understood despite recent progress in cellular and molecular aspects. Our primary aim is to analyze recent advances in understanding deviations in hepatic fat metabolism and the implication of gut physiology and microbiota in this transition. Our second aim is to gather experimental and clinical data on the capability of long-chain n-3 PUFA (LC n-3 PUFA), including docosahexaenoic (DHA) and eicosapentaenoic (EPA) acids to prevent or alleviate NAFLD. Our main conclusions are: (i) increasing data support a pivotal role for the gut toward NASH development; (ii) LC n-3 PUFA have often proven preventive or therapeutic effect toward NASH development in rodent models. In patients with NASH they appear to have no therapeutic effects, but they could have preventive effects, which require to define better the specific roles, modes of action, and doses of DHA and EPA.

Serum lipoprotein(a) [Lp(a)] in alcoholic men: Effect of withdrawal

This study examines the effect of alcohol withdrawal on lipoprotein(a) [Lp(a)] in 24 male, middle-aged chronic alcohol abusers admitted for withdrawal therapy. Serum concentration of Lp(a) was determined before and during the first 3 weeks of abstinence. The changes in three sialylated proteins [Lp(a), alpha 1-antitrypsin (alpha 1-AT), and haptoglobin (Hp)] and in desialylated transferrin (CDT) were also determined in 14 patients. After the 3 weeks of withdrawal therapy, the mean and median Lp(a) concentrations increased (p = 0.0001). The changes in Lp(a) levels were not related to the changes in dietary intake nor to the decrease in total HDL, HDL3, HDL2 cholesterol, Apo A-I, and Apo B. In the subgroup of 14 chronic alcohol abusers, Lp(a) levels increased parallel with Hp and alpha 1-AT, whereas CDT decreased. It is concluded that the impact of alcohol on sialylated proteins may be one of the mechanisms responsible for the increase in plasma Lp(a) after alcohol withdrawal.

Fish oil attenuates adrenergic overactivity without altering glucose metabolism during an oral glucose load in haemodialysis patients

Haemodialysis patients display an increased cardiac mortality, which may be partly related to increased sympathoadrenal activity and insulin resistance. Fish oil decreases adrenal activation induced by mental stress and has an insulin sensitizing effect in healthy subjects. Whole-body glucose metabolism after oral glucose was studied in eight haemodialysis patients before and after a 3-week oral fish oil supplementation (i.e. EPA + DHA at 1.8 g/d). Plasma glucose fluxes were traced by using [6,6- (2)H2]glucose infusion. Substrate oxidation was determined by using indirect calorimetry. Each patient was studied in the basal state and over the 6 h following absorption of a 1 g/kg glucose load. Energy expenditure in response to glucose re-increased over the last 2 h of the experiment (P < 0.05), which coincided with an increase in plasma catecholamines, especially epinephrine (P < 0.05), strongly suggesting a sympathoadrenal overactivity. Fish oil supplementation blunted both re-increase in thermogenic response and concomitant increase in plasma epinephrine, but not in plasma norepinephrine, over the last 2 h of the experiment. Fish oil did not alter either whole-body glucose metabolism or substrate oxidation. These data show that in haemodialysis patients, fish oil attenuates adrenal overactivity induced by oral glucose but does not modulate whole-body glucose metabolism and insulin sensitivity.

Interaction of low dose of fish oil and glucocorticoids on insulin sensitivity and lipolysis in healthy humans: A randomized controlled study.

SCOPE This study examined the interaction of fish oil (FO) with dexamethasone on glucose and lipid metabolisms in healthy subjects. METHODS AND RESULTS The study included two consecutive parts. Part A (randomized) in 16 subjects studied the effects of dexamethasone (2 days, 2 mg/day) versus placebo (lactose), part B (two parallel subgroups of eight) studied the interaction of FO (3 wk, 840 mg/day of EPA + DHA) with dexamethasone. Insulin sensitivity of lipolysis (d5-glycerol infusion + microdialysis), endogenous glucose production, and muscle glucose uptake were assessed by a three-step hot insulin clamp and substrate oxidation by indirect calorimetry. Dexamethasone induced liver and peripheral insulin resistance, an increase in fat oxidation, and a decrease in suppression of plasma nonesterified fatty acids (NEFAs). FO amplified the effects of dexamethasone by increasing liver and muscle insulin resistance, by reducing suppression of plasma NEFAs and fat oxidation and by increasing adipose tissue (AT) lipolysis. CONCLUSION FO, given at a moderate dose in healthy subjects prior to a very short-term (2 days) low dose of a synthetic glucocorticoid, worsened its deleterious effects on insulin sensitivity. The enhancing effect of FO on fat oxidation and AT lipolysis might be a protective effect toward an increase in fat mass.