Occasional physical inactivity combined with a high-fat diet may be important in the development and maintenance of obesity in human subjects.

BACKGROUND: A better understanding of the environmental factors that contribute to obesity is imperative if any therapeutic effect on the increasing prevalence of overweight and obesity in the United States is to be achieved. OBJECTIVE: This study examined the effect of the interaction of diet composition and physical inactivity on energy and fat balances. DESIGN: Thirty-five normal-weight and obese subjects were randomly assigned to either a 15-d isoenergetic high-carbohydrate (HC) or high-fat (HF) diet according to a crossover design. During the first 14 d, body weight and physical activity were maintained. On day 15, subjects spent 23 h in a whole-room indirect calorimeter and were fed a diet similar to that consumed during the previous 7 d while remaining physically inactive. RESULTS: Energy intakes required to maintain body weight stability during the first 14 d were similar between diets. Normal-weight and obese subjects consuming both diets had a positive energy balance on the sedentary day (day 15), suggesting that subjects were less active in the calorimeter. There was no significant effect of diet composition on total energy balance and total protein-energy balance on day 15; however, carbohydrate balance was more positive with the HC (2497.8 +/- 301.2 kJ) than with the HF (1159 +/- 301.2 kJ) diet (P = 0.0032). Most importantly, fat balance was more positive with the HF (1790.8 +/- 510.4 kJ) than with the HC (-62.8 +/- 510.4 kJ) diet (P = 0.0011). CONCLUSION: Chronic consumption of a high-carbohydrate diet could provide some protection against body fat accumulation in persons with a pattern of physical activity that includes frequent sedentary days.

Seasonal variation in lipoprotein lipase and plasma lipids in physically active, normal weight humans.

Adipose tissue lipoprotein lipase (ATLPL) provides free fatty acids (FFA) for storage in adipocytes, whereas in skeletal muscle LPL (SMLPL) provides FFA for oxidation. In hibernating animals, the level of SMLPL is relatively higher in summer than winter (promoting fat oxidation), whereas the opposite is seen with ATLPL. A patient-controlled study was designed to determine whether such seasonal variation occurs in normal weight humans. Eighteen subjects were studied in the summer and winter. After 2 days of a standardized diet, they underwent muscle and adipose biopsies for LPL activity, assessment of fitness by VO2 max, and determination of body composition by hydrostatic weighing. The percentages of body fat, body mass index, VO2 max, insulin, glucose, FFA, glycerol, and leptin were not affected by the season. Total cholesterol was higher in the winter than in the summer (157 +/- 5.5 vs. 148 +/- 4.2 mg/dL respectively; P = 0.03). The ATLPL activity was also higher in the winter than in the summer (4.4 +/- 0.8 vs. 2.3 +/- 0.6 nmol FFA/10(6) cells-min; P = 0.04). SMLPL activity trended to be higher in the winter than in the summer (1.9 +/- 0.5 vs. 1.0 +/- 0.1 nmol FFA/g x min; P = 0.06). In summary, ATLPL is seasonally regulated. It appears that SMLPL is similarly regulated by season. For physically active lean subjects, this increase in SMLPL may be a compensatory mechanism to help protect from seasonal weight gain.

Orlistat fails to alter postprandial plasma lipid excursions or plasma lipases in normal-weight male volunteers.

OBJECTIVES: After 10 d of orlistat administration (120 mg three times/day), the primary objective was to determine the drug's effect on postprandial plasma lipoprotein lipase (LPL) and hepatic triglyceride lipase (HTGL) activities on day 10 after an oral fat-load. The secondary objectives were to determine the effects of orlistat on 12 h postprandial measures of: (1) preheparin HTGL and LPL; and (2) serum triglycerides, very-low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol and free fatty acids. METHODS: Twenty-four normal-weight, healthy male volunteers were randomized to either 120 mg orlistat (n=12) or placebo (n=12) three times a day with meals for 10 d. Preheparin LPL and HTGL activities and LPL specific activity were measured in the fasted state on days 1, 5, and 10. On days 5 and 10 the study medication (orlistat or placebo) was taken at the beginning of a fat-rich breakfast and serum lipid and lipoprotein levels monitored for 12 h postprandially. On day 10, 15 min postheparin HTGL activity was measured 8 h after the fat-rich breakfast. RESULTS: No differences were found between groups in fasting levels of preheparin LPL or HTGL activity or in LPL-specific activity on days 1, 5 and 10. No difference was found between the two treatment groups in postheparin HTGL activity 8 h after the fat-rich breakfast. Also, no differences were found between the two groups in plasma triglycerides or lipoproteins. CONCLUSION: The results indicate that the oral administration of orlistat (120 mg t. i.d.) does not significantly alter plasma triglycerides or lipoproteins, and that the inhibitory effect of orlistat on lipases is limited to the gastrointestinal tract and is not manifested systemically.