Search PubMed⌕ Search

Biomedical subjects

D R Jensen

Publications and source records attributed to D R Jensen.

At least 37 records · Page 2Linked to original sources

Sustained weight reduction in moderately obese women results in decreased activity of skeletal muscle lipoprotein lipase.

Obesity is an increasingly prevalent problem, and long-term maintenance of the weight-reduced state is difficult for the obese individual. Following weight reduction, many metabolic changes occur. Among these is an increase in adipose tissue lipoprotein lipase (ATLPL), which predicts an alteration in lipid fuel partitioning which may then contribute to resumption of the obese state. The purpose of this study was to test whether changes in skeletal muscle LPL (SMLPL) and its response to insulin/glucose after sustained weight reduction also indicate a potential altered partitioning of lipid fuels away from oxidative pathways in muscle to storage in adipose tissue. Biopsies of vastus lateralis muscle were carried out in premenopausal obese women (n = 11, 94 +/- 4 kg, mean +/- SEM) before and after consumption of a 900 kcal day-1 diet for 3 months followed by 3 months of isocaloric maintenance of the reduced weight (n = 11, 82 +/- 4 kg). SMLPL activity was measured in the fasted state and after 6 h insulin/glucose infusion, before and after sustained weight loss. SMLPL activities were also measured in six normal weight women. Fasting SMLPL activity in obese women (3.9 +/- 0.3 nmol FFA min-1 g-1) was similar to that measured in normal weight control women (4.4 +/- 0.5). Unlike normal weight controls in whom a 6 h insulin/glucose infusion decreased SMLPL activity, in obese women the response of SMLPL was positive (normal weight vs. obese: delta -0.8 +/- 0.3 vs. delta 1.6 +/- 0.5, P = 0.002). Following maintained weight reduction, fasting SMLPL in the obese group was reduced to 1.2 +/- 0.3 (obese before weight loss vs. obese after: P = 0.0001). This change in fasting SMLPL activity following weight loss/maintenance correlated with the resultant change in percent body fat (r s = 0.663, P = 0.026).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Regulation of lipoprotein lipase activity and mRNA in the mammary gland of the lactating mouse.

We examined the effects of reproductive stage and fasting on lipoprotein lipase (LPL) activity and mRNA in the mouse mammary gland. Heparin-releasable and cell-associated LPL activity rose immediately after birth, followed 1-2 days later by an increase in LPL mRNA. Fasting decreased LPL activity in the mammary gland at all reproductive stages. During lactation, both milk and heparin-releasable LPL were substantially decreased by an overnight fast, whereas cell-associated LPL was less affected and LPL mRNA did not change. These studies indicate that the extracellular, heparin-releasable, fraction of mammary LPL activity responds most rapidly to alterations in physiological state, usually accompanied by smaller changes in cellular enzyme activity. Changes in the level of LPL mRNA were seen only during the transition from pregnancy to lactation, and these tended to follow, rather than precede, changes in enzyme activity. We conclude that in the mammary gland as in adipose tissue, LPL is regulated primarily at the translational and post-translational level.

Adipose Tissue↗

Macronutrient regulation of lipoprotein lipase is posttranslational.

To examine the relative impact of diet and meal composition on lipoprotein lipase (LPL), high fat (60% of energy) (HF) and high carbohydrate (68%) (HC) diets were fed to Sprague-Dawley rats for 2-3 wk, followed by overnight food deprivation and a meal of the same composition. Heparin-releasable LPL activities, mass and mRNA were measured in heart, diaphragm and soleus muscle and epididymal fat after food deprivation and 1, 2, 4 and 8 h postprandially. No effect of dietary macronutrient composition on LPL activity, protein or mRNA in food-deprived rats was demonstrated. However, in cardiac and diaphragm muscle, heparin-releasable LPL activity was suppressed by HC but stimulated by HF meal-feeding at 4 h. Moreover, in adipose tissue, the HC meal increased LPL activity at 1, 2 and 4 h relative to the basal period. Although there were no consistent effects of meal composition on LPL mass or mRNA in any one tissue, overall LPL mass was generally increased by HC meal-feeding. Because there were meal composition-dependent differences in LPL activity but no detectable differences in mass or mRNA in a particular tissue, LPL regulation by meals seems to be predominantly posttranslational.

Adipose Tissue↗

Tissue-specific lipoprotein lipase: relationships to body composition and body fat distribution in normal weight humans.

Twenty-six normal weight subjects (22 female, 4 male) were studied to determine the relationships of fasting levels of lipoprotein lipase in gluteal adipose tissue (ATLPL) and skeletal muscle (SMLPL) to body composition and body fat distribution. No relationship was found between fasting gluteal ATLPL and percent (%) body fat. There was, however, an inverse relationship between fasting SMLPL (from the vastus lateralis) and %body fat (p=0.005). A strong inverse correlation was also seen between fasting ATLPL and waist/hip ratio (p=0.0006), a measurement of body fat distribution. These relationships existed with or without the male subjects included. The tissue-specific relationships of lipoprotein lipase to body composition and body fat distribution could relate to the development of obesity or the maintenance of normal body weight by the effects of the lipase on the partitioning of lipoprotein triglyceride fatty acids.

Adipose Tissue↗

Relationship between skeletal muscle lipoprotein lipase activity and 24-hour macronutrient oxidation.

A low ratio of whole-body 24-h fat/carbohydrate (CHO) oxidation has been shown to be a predictor of subsequent body weight gain. We tested the hypothesis that the variability of this ratio may be related to differences in skeletal muscle metabolism. Since lipoprotein lipase (LPL) plays a pivotal role in partitioning lipoprotein-borne triglycerides to adipose (storage) and skeletal muscle (mostly oxidation), we postulated that a low ratio of fat/CHO oxidation was associated with a low skeletal muscle LPL (SMLPL) activity. As an index of substrate oxidation, 24-h RQ was measured under sedentary and eucaloric conditions in 16 healthy nondiabetic Pima males. During a 6-h euglycemic, hyperinsulinemic clamp, muscle biopsies were obtained at baseline, 3, and 6 h. Heparin-elutable SMLPL activity was 2.92 +/- 0.56 nmol free fatty acids/g.min (mean +/- SD) at baseline, was unchanged (2.91 +/- 0.51) at the third hour, and increased significantly (P < 0.05) to 3.13 +/- 0.57 at the sixth hour of the clamp. The mean (of baseline and 3-h) SMLPL activity correlated inversely with 24-h RQ (r = 0.57, P < 0.03) but not with body size, body composition, or insulin-mediated glucose uptake. Since SMLPL activity is related to the ratio of whole body fat/CHO oxidation rate, a decreased muscle LPL activity may, therefore, predispose to obesity.

Carbohydrate Metabolism↗

Distribution and source of lipoprotein lipase in mouse mammary gland.

During lactation lipoprotein lipase (LPL) is elevated in mammary tissue and depressed in adipose tissue to redirect lipids for incorporation into milk fat. The cellular origin of lipoprotein lipase in mammary tissue is thought to be the mammary epithelial cell which is the predominant cell type noticeable in the lactating gland; however, mammary adipocytes are also present. If lipoprotein lipase is produced by adipocytes in other sites of the body, then the question remains as to why mammary adipocytes have not been shown to produce lipoprotein lipase. In this study we present several lines of evidence that indicate that the mammary adipocyte is a source of LPL in the lactating mammary gland of mice. This evidence includes the absence of extracellular and intracellular lipoprotein lipase activity in two types of primary mammary epithelial cell cultures and a similarity in the changes of lipoprotein lipase activity in genital adipose tissue from nonpregnant mice and lactating mammary tissue to the nutritional state of the animal. Other evidence presented here includes strong localization of lipoprotein lipase protein and messenger RNA by fluorescence immunohistochemistry and in situ hybridization, respectively, to interstitial cells located between epithelial structures. We postulate that these interstitial cells are regressed, lipid-deleted mammary adipocytes.

Adipose Tissue↗

Effects of ingested gossypol on the ultrastructure of rat ovarian follicles.

Ultrastructural changes were observed in the oocytes and granulosa cells of the ovarian follicles of sexually mature female rats treated daily for 60 days with gossypol acetic acid at a dosage known to induce sterility in male rats (20 mg/kg body weight, orally). The changes included an increased lysosomal population in the ooplasm and a reduced, poorly developed smooth endoplasmic reticulum in the granulosa cells. The latter changes suggest a suppression of the secretory activity of the granulosa cells.

Administration, Oral↗

Radioiron utilization and gossypol acetic acid in male rats.

The 24-h incorporation of 59Fe into circulating red blood cells, bone marrow, urine, liver, spleen, and skeletal muscle was measured in splenectomized and sham-splenectomized rats which had received a daily, oral dose of gossypol acetic acid (20 mg GAA/kg body wt) for 91 days. A significant decrease in total body weight gain was observed in all GAA treated animals. Splenectomized rats dosed with GAA exhibited a significant decrease in hemoglobin concentration, hematocrit and erythrocyte count. A significant increase in 59Fe incorporation by red blood cells and a decrease in hepatic incorporation of 59Fe indicate a preferential utilization of iron in erythropoiesis among GAA treated animals.

Animals↗

Multiple comparisons in the randomization analysis of designed experiments with growth curve responses.

A randomization approach to multiple comparisons is developed for comparing several growth curves in randomized experiments. The exact Type I probability error rate for these comparisons may be prespecified, and a Type I error probability for each component test can be evaluated. These procedures are free of many of the standard assumptions for analyzing growth curves and for making multiple comparisons. An application of the procedure gives all pairwise comparisons among the mean growth curves associated with four treatments in an animal experiment using a Youden square design, where growth curves are obtained on monitoring hormone levels over time.

Animals↗

Deposition pattern of the antifertility agent, gossypol, in selected organs of male rats.

Male rats received daily, oral doses of gossypol-acetate (40 mg/kg body wt) for 2, 4, or 8 weeks to determine patterns of gossypol deposition in the spleen, liver, heart, kidneys, lungs, and testes during establishment of a gossypol-induced infertility. Infertility was exhibited at the end of the 4-week dosing period. Free and bound gossypol accumulated in all of the organs.

Animals↗

Efficiency and robustness in the use of repeated measurements.

Efficiencies in repeated-measurements experiments are studied by the use of F statistics when appropriate and of Hotelling's T2 statistics otherwise. Bounds on the asymptotic relative efficiencies of these statistics are given and conditions are found under which one test dominates another uniformly. Similar comparisons are made between T2 and the Lawley-Hotelling T2(0) test in the analysis of repeated vector measurements. It is found that the T2 test may be considerably more efficient than its competitors, but that its efficiency cannot be substantially less. These findings are illustrated numerically by examples from the literature. It is shown further that F and T2 tests are exact for all unimodal distributions constant on ellipsoids, and that efficiency comparisons among F tests are preserved under scale mixtures of multidimensional Gaussian laws.

Humans↗

Scanning electron microscopic study of spermatozoa from gossypol-treated rats.

Spermatozoa from the cauda epididymidis of gossypol-treated rats exhibit distinctive departures from the morphology of spermatozoa from control rats: wrinkled and disorganized cell membrane in the head and tail regions, cell membrane missing from segments of the tail midpiece and principal piece regions, malformed heads, decapitate spermatozoa, retention of a cytoplasmic droplet at variable loci along tail midpieces, and looped tails. The observations suggest that gossypol exerts its contraceptive effect during spermatocytogenesis and spermiogenesis, including the posttesticular development and maturation of spermatozoa in the epididymis.

Animals↗