Characterization of lipase activities in obese Pima indians. Decreases with weight reduction.

Adipose tissue and muscle lipoprotein lipase and postheparin hepatic and lipoprotein lipase activities have been measured in a group of 21 Pima Indian males over a wide range of body weight to determine the relationship between obesity and these lipase activities. There was a significant positive correlation between adipose tissue lipoprotein lipase and obesity; muscle and postheparin lipoprotein lipase and hepatic lipase were not related to degree of obesity. Fasting insulin levels were not related to any of the measurements of lipase activity. There were racial differences in adipose and postheparin lipoprotein lipase activities; both were significantly lower in the Pimas as compared with a group of weight-matched Caucasian males. Lipase activities were remeasured in eight subjects after a period of weight reduction including several weeks of stabilization at the reduced weights. After the period of weight reduction adipose tissue lipoprotein lipase declined in all subjects. Hepatic lipase also declined in all but two patients. Muscle and postheparin lipolytic activities were not affected by weight loss. The data indicate that (a) there are racial differences in adipose tissue lipoprotein lipase; and (b) the elevated adipose lipoprotein lipase associated with obesity, like many other biochemical variables in the obese state, returns toward normal after weight reduction.

Very-low-density lipoprotein triglyceride metabolism in non-insulin-dependent diabetes mellitus. Relationship to plasma insulin and free fatty acids.

To investigate the mechanism of elevated plasma triglycerides in non-insulin-dependent (type II) diabetes, very-low-density lipoprotein triglyceride (VLDL-TG) metabolism was studied in 10 untreated male Pima Indian diabetics and compared with that of 15 weight-matched male nondiabetic controls. VLDL-TG metabolism was studied using tritiated glycerol as an endogenous precursor of VLDL-TG, and the resultant kinetic data were analyzed using a multicompartmental model, which includes two pathways for VLDL-TG synthesis and a stepwise delipidation process for VLDL catabolism. Pima diabetics had VLDL-TG concentrations approximately 150% those of nondiabetics. Rates of VLDL-TG production in the diabetics were not significantly different from those of controls. On the other hand, the fractional catabolic rate for VLDL-TG was significantly lower in the diabetics compared with the nondiabetics. Other catabolic parameters, such as the fraction of VLDL-TG delipidized at each step and the stepwise delipidation rate, were also decreased in the diabetics. To determine the relationships between the increased triglycerides and determinants of lipid metabolism that are altered in diabetes, insulin and free fatty acid concentrations were also assessed. Basal C-peptide levels in the diabetics during the metabolic study were slightly but not significantly higher than those of the nondiabetics. There was a highly significant correlation in the diabetics between plasma C-peptides and VLDL-TG production, whereas VLDL production in Pima nondiabetics was not related to insulin levels. Free fatty acid levels were not significantly elevated in the Pima diabetics. The data indicate that (1) the rise in VLDL-TG in Pima diabetics was a result of decreased capacity for clearance and (2) the absence of elevated VLDL-TG production may be attributed to the lack of increase in free fatty acids.

Improvement of glucose homeostasis after exercise training in non-insulin-dependent diabetes.

Six obese patients with recent-onset, non-insulin-dependent diabetes underwent assessment of glucose tolerance, insulin secretory capacity, and insulin-induced glucose disposal before and after 6-10 wk of intensive aerobic training while maintaining body weight. Fasting plasma glucose declined in every subject (average = -33 mg/dl), and oral glucose tolerance (3 h integrated plasma glucose) improved in five of the six (average = -74 mg X 3 h/dl) after training. Individual improvement in control of plasma glucose was directly proportional to degree of hyperglycemia before training and correlated well with an observed improvement in the early (30-min) plasma insulin response to oral glucose (all six subjects). The response of insulin action to training was highly variable; although the observed increase in average insulin-induced glucose disposal rate (M) during the euglycemic clamp did not reach statistical significance in our small cohort, the relative change in M was directly related to reduction in fasting insulin levels after training. Our results show that regular endurance exercise is effective in improving glucose homeostasis and may serve as an adjunct to other modes of treatment in recent-onset, non-insulin-dependent diabetic individuals.

Yucatan miniature swine as a model for diet-induced atherosclerosis.

Nine female Yucatan miniature swine, a breed not previously evaluated for their potential usefulness as a model for experimental atherosclerosis studies, were fed a high-fat, high-cholesterol diet for 10-12 months. These swine and 4 control (low-fat, low-cholesterol-fed) swine underwent a complete necropsy at the end of this period to characterize the atherosclerosis both by gross and microscopic examination. Cholesterol feeding led to elevated serum cholesterol levels and the development of accelerated atherosclerosis. Control animals on a low-cholesterol diet had little gross or microscopic atherosclerosis. All of the cholesterol-fed swine had more extensive atherosclerosis than any of the controls by gross inspection of the Sudan-stained arterial tissue. There was individual variation suggesting the interaction of factors in addition to the plasma cholesterol which determine the extent and severity of atherosclerosis. However, it was possible to show a positive correlation between hypercholesterolemia and (1) intimal thickening in the terminal abdominal aorta and mesenteric artery, and (2) increased fat deposition in the mesenteric artery. The cholesterol-induced atherosclerosis was characterized by the deposition of lipid in and around cells. Complicated atherosclerotic lesions similar to human atherosclerosis were characterized by marked animal proliferation, necrosis, cholesterol crystal deposition, and calcification. It is concluded that the Yucatan miniature swine represent an important additional animal model in which to study certain aspects of atherosclerosis.

Perinatal hospice: a response to partial birth abortion for infants with congenital defects.

This article discusses decisions involving whether to terminate late-term pregnancies when fetal anomalies have been detected. Partial-birth abortion performed on fetuses with chromosomal abnormalities, while performed under the guise of reducing suffering, threatens the best interests of the mother and infant. An alternative for parents faced with the decision to terminate their pregnancy is perinatal hospice. Perinatal hospice recognizes the value of bringing these infants to term by treating them as beings conceived with a tangible future. This alternative is preferred because of post-termination psychological distress and because biblical teachings emphasize the dignity and worth of each fetus. Perinatal hospice supports parents through their grief when their infant dies and maximizes the opportunity for authentic mourning.

Quantitative measures of enzyme activities in type I and type II muscle fibres of man after training.

The effect of 7 to 8 weeks of physical training on oxidative and glycolytic enzyme activities in the 2 major fibre types of human quadriceps femoris muscle has been investigated. 2 groups of 4 and 5 subjects respectively were trained at the same total work-load on a bicycle ergometer 3 days per week using interval exercise with maximal intensity (I.T.) or continuous exercise with submaximal intensity (C.T.). Succcinate dehydrogenase (SDH) and phosphofructokinase (PFK) activities were determined on crude homogenates of muscle biopsy samples and on pools of type I and type II fibres dissected from freeze-dried samples taken before and after training. Crude homogenate SDH activity increased to the same extent in both groups, average increases were 27.5% (I.T.) and 22% (C.T.) respectively. Only type I-SDH increased in the C.T. group (p less than 0.01), the average increase being 32%. On the other hand only type II-SDH increased in the I.T. group (p less than 0.01), with an average increase of 49%. No changes in PFK activity could be detected. The results of the present study emphasize the great adaptability in oxidative potential of both the two major human skeletal muscle fibre types and further that this adaptation seems to be related to the pattern of fibre recruitment during exercise.

Time course of changes in human skeletal muscle succinate dehydrogenase and cytochrome oxidase activities and maximal oxygen uptake with physical activity and inactivity.

Succinate dehydrogenase (SDH) and cytochrome oxidase activities in the lateral vastus of the human quadriceps femoris muscle together with total body VO2 max were followed during an 8-10 week period of endurance training (n = 13) and a successive 6 week period without training (n = 8). During the training period there was a gradual increase in both VO2 max and muscle oxidative enzyme activities, all being significantly different from the pre-training levels after 3 weeks of training. After 8 weeks of training VO2 max was 19%, vastus lateralis SDH 32%, and cytochrome oxidase activity 35% above the pre-training levels respectively. 6 weeks post training VO2 max was still 16% above the pre-training level, and not significantly different from the level at the end of training (p greater than 0.2). In contrast vastus lateralis SDH activity had returned to the pre-training level. Cytochrome oxidase activity had returned to the pre-training level within two weeks post-training. The significantly faster post-training decline in skeletal muscle oxidative enzyme activities in contrast to that of the VO2 max indicates that an enhancement of the oxidative potential in skeletal muscle is not a necessity for a high VO2 max. Moreover, the fast return to the pre-training level of both SDH and cytochrome oxidase activities indicate a high turnover rate of enzymes in the TCA cycle as well as the respiratory chain.