Effects of equal weight loss with orlistat and placebo on body fat and serum fatty acid composition and insulin resistance in obese women.
BACKGROUND
Dietary fat has been reported to influence insulin sensitivity.


OBJECTIVE
The objective of the study was to determine how identical weight loss (target: loss of 8% of body weight over 3-6 mo) in women taking orlistat or placebo combined with a hypocaloric diet influences body composition and insulin sensitivity.


METHODS
Forty-seven obese women [body mass index (in kg/m(2)): 32.1 +/- 0.4] were randomly assigned to receive either orlistat (120 mg 3 times daily; n = 23) or placebo (n = 24) with a hypocaloric diet. Whole-body insulin sensitivity (insulin clamp technique), serum fatty acids, and body composition (magnetic resonance imaging) were measured before and after weight loss.


RESULTS
The groups did not differ significantly at baseline with respect to age, body weight, intraabdominal and subcutaneous fat volumes, or insulin sensitivity. Weight loss did not differ significantly between the orlistat (7.3 +/- 0.2 kg, or 8.3 +/- 0.1%) and placebo (7.4 +/- 0.2 kg, or 8.2 +/- 0.1%) groups. Insulin sensitivity improved significantly (P < 0.001) and similarly after weight loss in the orlistat (from 4.0 +/- 0.3 to 5.1 +/- 0.3 mg x kg fat-free mass(-1) x min(-1)) and placebo (from 4.4 +/- 0.4 to 5.4 +/- 0.4 mg x kg fat-free mass(-1) x min(-1)) groups. Intraabdominal fat and subcutaneous fat decreased significantly in both groups, but the ratio of the 2 decreased significantly only in the orlistat group. The proportion of dihomo-gamma-linolenic acid (20:3n-6) in serum phospholipids was inversely related to insulin sensitivity both before (r = -0.48, P < 0.001) and after (r = -0.46, P < 0.001) weight loss, but it did not change significantly in either group.


CONCLUSIONS
Weight loss rather than inhibition of fat absorption enhances insulin sensitivity. A decrease in fat absorption by orlistat appears to favorably influence the ratio between intraabdominal and subcutaneous fat, which suggests that exogenous fat or its composition influences fat distribution.
Tiikkainen
Mirja
M
Division of Diabetes, Department of Medicine, University of Helsinki, Finland.
Bergholm
Robert
R
Rissanen
Aila
A
Aro
Antti
A
Salminen
Irma
I
Tamminen
Marjo
M
Teramo
Kari
K
Yki-Järvinen
Hannele
H
D000328:Adult; D019440:Anti-Obesity Agents / Q000627:therapeutic use*; D001794:Blood Pressure; D015992:Body Mass Index; D004038:Diet, Reducing; D004041:Dietary Fats / Q000008:administration & dosage; D005227:Fatty Acids / Q000097:blood*; D005260:Female; D006801:Humans; D007333:Insulin Resistance; D007783:Lactones / Q000627:therapeutic use*; D008875:Middle Aged; D009765:Obesity / Q000178:diet therapy / Q000188:drug therapy*; D000077403:Orlistat; D015431:Weight Loss
D019440:Anti-Obesity Agents; D004041:Dietary Fats; D005227:Fatty Acids; D007783:Lactones; D000077403:Orlistat