Obesity is a major health concern in the United States. Studies in both animals and humans indicate that deviations of body weight results in compensatory changes in energy balance with return of weight to baseline. Although it remains unclear as to whether mechanisms that results in weight gain following weight reduction are identical to those contributing to the etiology of obesity, increases in insulin sensitivity may be operational. Lipoprotein lipase (LPL) is a multi-functional enzyme produced by a number of tissues, most importantly adipose tissue and muscle. In general, meals high in carbohydrate (CHO) stimulate adipose tissue LPL (ATLPL) whereas meals high in fat stimulate skeletal muscle LPL (SMLPL). This may be relevant to body weight maintenance in that the partitioning of lipid fuels between adipose tissue and muscle may depend on the tissue-specific regulation of LPL by diet. These tissue-specific changes in LPL regulation by meals may also relate to insulin sensitivity. In lean subjects, insulin increases ATLPL, but fails to change or decreases SMLPL. However, in obesity, the dose- response curve for ATLPL stimulation by insulin is shifted to the right whereas SMLPL is now increased rather than decreased by insulin. These changes are consistent with a metabolic environment of insulin resistance in which partitioning of lipid fuels is away from storage in adipose tissue to oxidation in skeletal muscle. Studies to be carried out will determine in normal weight human subjects if the effects of a high CHO vs. high fat diet/meal on tissue-specific LPL responsiveness will predict weight stability vs. weight gain over 4 years. It is expected that a diet high in CHO meal. Also postulated is that a high fat diet will increase the SMLPL response to a high fat meal. The metabolic effect of diet/meal on LP in tissues will also be examined by measurements of 14C recovery in expired air and adipose tissue following ingestion of a 14C- triolein meal. It is expected that these changes in tissue-specific LPL responsiveness to diet/meals will relate both to changes in respiratory quotient (RQ) and to insulin responsiveness with relative insulin sensitivity predicting weight gain and relative insulin resistance weigh stability. A similar study will be carried out in obese subjects where it is expected that a diet high in CHO will fail to increase ATLPL responsiveness, but will increase SMLPL responsiveness to a high CHO meal. This could be a metabolic adaptation which would serve to maintain the obese weight. Moreover, it is expected that a high fat diet will increase the responsiveness of SMLPL to a high fat meal more so than in normal weight subjects. As in normal weight subjects, the metabolic effect of diet/meal or LPL in tissues will also be examined by measurement of 14C recovery following ingestion of a 14C-triolient meal. In obese subjects, tissue-specific LPL responsiveness to diet/meal will also be expected to correlate with changes in RQ and insulin responsiveness, with relative insulin sensitivity predicting weight gain and relative insulin resistance weight stability. If obesity-prone individuals could be identified by their metabolic response to diet, a preventive program could be better targeted and the incidence of obesity hopefully reduced.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK046881-02
Application #
2146154
Study Section
Nutrition Study Section (NTN)
Project Start
1994-08-15
Project End
1999-07-31
Budget Start
1995-08-01
Budget End
1996-07-31
Support Year
2
Fiscal Year
1995
Total Cost
Indirect Cost
Name
University of Colorado Denver
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
065391526
City
Aurora
State
CO
Country
United States
Zip Code
80045
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Eckel, Robert H; Hernandez, Teri L; Bell, Melanie L et al. (2006) Carbohydrate balance predicts weight and fat gain in adults. Am J Clin Nutr 83:803-8
Shepard, T Y; Weil, K M; Sharp, T A et al. (2001) Occasional physical inactivity combined with a high-fat diet may be important in the development and maintenance of obesity in human subjects. Am J Clin Nutr 73:703-8