A 2-year multifactor approach of weight loss maintenance.

The overarching problem in the treatment of obesity is the consistency with which weight in treatment is regained. The aim of this study is to follow-up the patient using a multifactor approach (cognitive-behavioral therapies, diet and physical activity counselling, an "on-off" prescription of orlistat) during 4 years in order to assess the efficacy of this specific long-term weight loss maintenance programme. Weight maintenance is defined as a weight change of <2.5% of the study entry body weight. Fifty obese patients having previously lost at least 10% of their weight by any weight loss programme before entering the maintenance multifactor approach were enrolled. Ninety percent of the patients maintained more than 10% weight loss after 2 years. All the physical characteristics remained similar between study entry and 2 years after the weight loss maintenance programme. Waist and hip as well as fat mass did not show any significant differences and the mean fat mass remained stable 2 years later. In addition, all the psychological parameters analysed remained stable and in a normal range. In conclusion, this multifactor approach shows promising interim results at year-2. The multifactor approach with an "on-off" prescription of orlistat seems to be appropriate for the long term weight loss maintenance. But considering the clinical and psychological diversity of the patients, this approach has to be individually adapted for patients presenting eating behavior disorders which need a particular follow-up.

[Long term weight loss maintenance]. / Maintien de la perte de poids à long terme.

A successful weight loss program leads to a new metabolic and endocrine balance that needs new long term management. Recent researches have shown some predictors as well as some barriers of the long term weight management. Predictors and barriers are linked to the lost weight, to the subject's habits and to the patient's psychosocial sphere. During the four-year follow-up, 78% of patients maintained 10% or more of their initial weight loss. The patients who maintained their weight presented less binge eating disorder, good motivation in diet and physical activity.

Upregulation of peroxisome proliferator-activated receptor gamma coactivator gene (PGC1A) during weight loss is related to insulin sensitivity but not to energy expenditure.

AIMS/HYPOTHESIS: We investigated whether skeletal muscle peroxisome proliferator-activated receptor gamma coactivator-1 (PGC1A; also known as PPARGC1A) and its target mitofusin-2 (MFN2), as well as carnitine palmitoyltransferase-1 (CPT1; also known as carnitine palmitoyltransferase 1A [liver] [CPT1A]) and uncoupling protein (UCP)3, are involved in the improvement of insulin resistance and/or in the modification of energy expenditure during surgically induced massive weight loss. MATERIALS AND METHODS: Seventeen morbidly obese women (mean BMI: 45.9 +/- 4 kg/m(2)) were investigated before, and 3 and 12 months after, Roux-en-Y gastric bypass (RYGB). We evaluated insulin sensitivity by the euglycaemic-hyperinsulinaemic clamp, energy expenditure and substrate oxidation by indirect calorimetry, and muscle mRNA expression by PCR. RESULTS: Post-operatively, PGC1A was enhanced at 3 (p = 0.02) and 12 months (p = 0.03) as was MFN2 (p = 0.008 and p = 0.03 at 3 and 12 months respectively), whereas UCP3 was reduced (p = 0.03) at 12 months. CPT1 did not change. The expression of PGC1A and MFN2 were strongly (p < 0.0001) related. Insulin sensitivity, which increased after surgery (p = 0.002 at 3, p = 0.003 at 12 months), was significantly related to PGC1A and MFN2, but only MFN2 showed an independent influence in a multiple regression analysis. Energy expenditure was reduced at 3 months post-operatively (p = 0.001 vs before RYGB), remaining unchanged thereafter until 12 months. CPT1 and UCP3 were not significantly related to the modifications of energy expenditure or of lipid oxidation rate. CONCLUSIONS/INTERPRETATION: Weight loss upregulates PGC1A, which in turn stimulates MFN2 expression. MFN2 expression significantly and independently contributes to the improvement of insulin sensitivity. UCP3 and CPT1 do not seem to influence energy expenditure after RYGB.

Relationship between sympathetic reactivity and body weight loss in morbidly obese subjects.

OBJECTIVE: To investigate the possible role of peripheral sympathetic activity in gastric bypass-induced body weight loss. SUBJECTS AND METHODS: In 42 morbidly obese patients (sex: 36 f/6 m; BMI: 46.0+/-0.7 kg/m(2)) undergoing a gastric bypass, the skin vasoconstrictor reflex in answer to a deep inspiration was measured by laser Doppler fluximetry. The extent of vasoconstriction, measured at the second finger of the left hand, was expressed as percent reduction of the basal blood flux (% vasoconstriction). Insulin sensitivity was assessed before surgery in a subset of patients (n=11), by the method of euglycemic, hyperinsulinemic clamp. Body weight and composition were evaluated before, and 3, 6 and 12 months after surgery. At the same time points, energy intake (kJ/day) was evaluated by means of both food record diary and alimentary anamnesis. RESULTS: The % vasoconstriction, which was significantly (P=0.01) greater in normoglycemic subjects than in diabetic ones, was also significantly (P=0.03) related to the extent of insulin sensitivity measured during the euglycemic clamp. The % vasoconstriction showed a significant (P>0.0001), positive correlation with weight reduction obtained between the 6th and 12th months following surgery; as a consequence, % vasoconstriction was significantly (P=0.0004) related to the overall body weight loss achieved during the year following the operation. These correlations remained significant in multiple regression analysis with adjustment for age, initial body weight, plasma glucose and insulin (P=0.0007 and 0.006, respectively). The % vasoconstriction was also significantly (P=0.0006), negatively related to energy intake measured 12 months after surgery. CONCLUSIONS: In conditions of stable body weight, the sympathetic nervous system (SNS) reactivity is influenced by the degree of insulin resistance. A high capacity to activate the SNS, measured before surgery, is associated with both a larger gastric bypass-induced weight loss and a lower energy intake, at the phase of weight stabilization.

Beneficial effect of hormone replacement therapy on weight loss in obese menopausal women.

OBJECTIVE: At the onset of menopause, weight-gain and the aggravation of certain cardiovascular risk factors are frequently observed. The aim of this study was to examine the metabolic effects of combined hormone replacement therapy (17beta-oestradiol transdermic 50 microg for 21 days and oral medroxyprogesterone acetate 5 mg from day 10 to 21) using, in particular, indirect calorimetry. METHODS: Patients (21; 12 substituted and nine controls) were studied twice (3 months apart) during an oral glucose load (75 g). RESULTS: Total body weight was unaltered after 3 months in the control group, whereas a fat-loss of 2.1+/-0.2 kg and a decrease of the waist:hip ratio were observed in the substituted group. In the latter group, a significant increase in lipid oxidation was observed (0.58+/-0.06 mg/kg/min before and 0.75+/-0.04 mg/kg/min after substitution P<0.05), whilst total energy expenditure and thermogenesis were also increased. Glucose, lipid and protein oxidation remained stable during three months in the control group. The insulin response to an oral glucose load diminished by 30% with hormone replacement therapy (102.3+/-32.8 mmicro/l versus 71.4+/-20.0 mmicro/l). Total and LDL-cholesterol improved after hormone replacement therapy whereas plasma triglycerides were not altered. CONCLUSIONS: Combined hormone replacement therapy not only prevented weight-gain, but favored weight-loss by significantly increasing lipid oxidation after 3 months of treatment. It also favourably influenced the insulin response, plasma lipids and energy expenditure.

Energy expenditure and substrates oxidative patterns, after glucose, fat or mixed load in normal weight subjects.

OBJECTIVES: To evaluate energy balance after three isocaloric oral loads of different composition and to establish possible relationships between the substrates oxidative patterns and the modifications of insulin and free fatty acids (FFA) plasma profiles. DESIGN: Each subject received, in a randomized order, three oral loads of 2658 +/- 45 kJ (636 +/- 11 Kcal) either as glucose, lipids (cream) or a mixture (glucose+cream). SETTING: The experiments were performed at the University Hospital of Geneva. SUBJECTS: Ten normal body-weight volunteers. METHODS: Energy expenditure (EE) and substrates oxidation were measured by indirect calorimetry during 8 h following each load. Plasma glucose, insulin and FFA were also measured. RESULTS: EE was 1776 +/- 107, 1818 +/- 125 and 1785 +/- 117 KJ over 8 h after glucose, mixed and lipids load, respectively. Glucose oxidation was the highest after oral glucose as compared to mixed and lipids load, while the highest value of lipids oxidation was measured after fat load. A significant relationship linked fat oxidation to plasma FFA (r = 0.54, P < 0.002) as well as to insulin (r = -0.40, P < 0.002). CONCLUSIONS: (a) The energetic cost of glucose and fat intake is the same; (2) after each load, the main source of energy corresponds to the substrate administered; (3) both plasma insulin and FFA influence the substrate oxidative patterns observed after each load; (4) alimentary fat may contribute to fat oxidation by maintaining elevated plasma FFA levels.