Long chain fatty acid transport is selectively up-regulated in adipocytes of Zucker fatty rats, diverting fatty acids from sites of oxidation toward storage in adipose tissue. To determine whether this is a general feature of obesity, we studied [ 3 H]oleate uptake by adipocytes and hepatocytes from 1) homozygous male obese (ob), diabetic (db), fat (fat), and tubby (tub) mice and from 2) male Harlan Sprague-Dawley rats fed for 7 weeks a diet containing 55% of calories from fat. V max and K m were compared with controls of the appropriate background strain (C57BL/6J or C57BLKS) or diet (13% of calories from fat). V max for adipocyte fatty acid uptake was increased 5-6-fold in ob, db, fat, and tub mice versus controls (p < 0.001), whereas no differences were seen in the corresponding hepatocytes. Similar changes occurred in fat-fed rats. Of three membrane fatty acid transporters expressed in adipocytes, plasma membrane fatty acid-binding protein mRNA was increased 9 -11-fold in ob and db, which lack a competent leptin/leptin receptor system, but was not increased in fat and tub, i.e. in strains with normal leptin signaling capability; fatty acid translocase mRNA was increased 2.2-6.5-fold in tub, ob, and fat adipocytes, but not in db adipocytes; and only marginal changes in fatty acid transport protein 1 mRNA were found in any of the mutant strains. Adipocyte fatty acid uptake is generally increased in murine obesity models, but up-regulation of individual transporters depends on the specific pathophysiology. Leptin may normally down-regulate expression of plasma membrane fatty acid binding protein.In normal man and most mammalian species, body weight is maintained within narrow limits through regulation of both caloric intake and energy expenditure (1, 2). If caloric intake persistently exceeds energy expenditure, obesity is an inevitable consequence. However, there are obvious differences in the tendency to obesity among individuals with seemingly equivalent caloric intake and similar degrees of physical activity (3). Likewise, there are differences among rat strains in the propensity to develop obesity on high fat diets (4). Finally, a number of single-gene mutations that lead to obesity in mice and rats have been identified and cloned (5-13), leading in several instances to elucidation of the mechanisms underlying phenotypic expression. Studies in these animal models and in obese humans have led to the concepts of energy efficiency and of nutrient partitioning as being important physiological mechanisms underlying individual or strain differences in the propensity to become obese (1,14,15).Individuals with high energy efficiency require fewer calories to meet basal metabolic needs and accomplish a given level of physical work. Thus, on a given caloric intake, more calories are, in essence, left over, and are stored as fat. Individuals with low energy efficiency utilize more of their caloric intake for basal metabolism and physical work, leaving fewer calories for storage as fat. The factors responsible for dif...

We have used the ciliate Euplotes to study the role of DNA polymerase in telomeric C strand synthesis. Euplotes provides a unique opportunity to study C strand synthesis without the complication of simultaneous DNA replication because millions of new telomeres are made at a stage in the life cycle when no general DNA replication takes place. Previously we showed that the C-strands of newly synthesized telomeres have a precisely controlled length while the G-strands are more heterogeneous. This finding suggested that, although synthesis of the G-strand (by telomerase) is the first step in telomere addition, a major regulatory step occurs during subsequent C strand synthesis. We have now examined whether G-and C strand synthesis might be regulated coordinately rather than by two independent mechanisms. We accomplished this by determining what happens to G-and C strand length if C strand synthesis is partially inhibited by aphidicolin. Aphidicolin treatment caused a general lengthening of the G-strands and a large increase in C strand heterogeneity. This concomitant change in both the G-and C strand length indicates that synthesis of the two strands is coordinated. Since aphidicolin is a very specific inhibitor of DNA pol␣ and pol␦, our results suggest that this coordinate length regulation is mediated by DNA polymerase. INTRODUCTIONIn most organisms telomere length is determined by a balance between activities that elongate and shorten the telomeric DNA (Greider, 1996). Telomere shortening is caused by incomplete replication of the 5Ј end of the chromosome or by nuclease action, whereas elongation is caused either by telomerase, the specialized terminal transferase that extends the G-rich strand of the telomere, or by recombination. The balance between telomere lengthening and shortening is extremely important for long-term cell viability as continuous telomere lengthening or shortening results in increased cell death (Lundblad and Szostak, 1989;McEachern and Blackburn, 1995;Krauskopf and Blackburn, 1996;Wright et al., 1996). For example, in human somatic cells the absence of telomerase leads to progressive loss of telomeric DNA at each population doubling until the cells eventually become senescent and die (Greider, 1996;Wright et al., 1996). A similar effect is observed in yeast where mutations in telomerase components or telomere proteins lead to telomere shortening and senescence (Singer and Gottschling, 1994;Nugent et al., 1996;Virta-Pearlman et al., 1996). Genetic experiments in yeast have shown that telomere length regulation is a complex process that involves many different molecules. For example, telomere length is affected by mutations not only in telomerase, but also in telomere-binding proteins, the DNA replication machinery, helicases, and check point-related proteins (Carson and Hartwell, 1985;Schulz and Zakian, 1994;Singer and Gottschling, 1994;Morrow et al., 1995;Zakian, 1995;Adams and Holm, 1996;Nugent et al., 1996;Virta-Pearlman, 1996;Cooper et al., 1997). One general theme to emerge is that telo...

OBJECTIVE:To determine the impact of obesity on adipocyte cell size and long-chain fatty acid (LCFA) uptake kinetics in human subjects undergoing laparoscopic abdominal surgery. SUBJECTS: A total of 10 obese patients (BMI 49.8711.9 (s.d.) kg/m 2 ) undergoing laparoscopic bariatric surgery, and 10 nonobese subjects (BMI 24.272.3 kg/m 2 ) undergoing other clinically indicated laparoscopic abdominal surgical procedures. MEASUREMENTS: Cell size distribution and [ 3 H]oleic acid uptake kinetics were studied in adipocytes isolated from omental fat biopsies obtained during surgery. Adipocyte surface area (SA) was calculated from the measured cell diameters. Plasma leptin and insulin concentrations were measured by RIA in fasting blood samples obtained on the morning of surgery. RESULTS: The mean SA of obese adipocytes (41 50875381 m 2 /cell) was increased 2.4-fold compared to that of nonobese adipocytes (16 92876529 m 2 /cell; Po0.01). LCFA uptake in each group was the sum of saturable and nonsaturable components. Both the V max of the saturable component (21.376.3 vs 5.171.9 pmol/s/50 000 cells) and the rate constant k of the nonsaturable component (0.01570.002 vs 0.006670.0023 ml/s/50 000 cells) were increased (Po0.001) in obese adipocytes compared with nonobese controls. When expressed relative to cell size, V max /m 2 SA was greater in obese than nonobese adipocytes (Po0.05), whereas k/m 2 SA did not differ between the groups. CONCLUSION: The data support the concepts that (1) adipocyte LCFA uptake consists of distinct facilitated (saturable) and diffusive processes; (2) increased saturable LCFA uptake in obese adipocytes is not simply a consequence of increased cell size, but rather reflects upregulation of a facilitated transport process; and (3) the permeability of adipocyte plasma membranes to LCFA is not appreciably altered by obesity, and increased nonsaturable uptake in obese adipocytes principally reflects an increase in cell SA. Regulation of saturable LCFA uptake by adipocytes may be an important control point for body adiposity.

BE is a male-dominant disease. The prevalence of Barrett's esophagus was not significant different among Caucasian, Hispanics, and African Americans. Most of the patients with BE, dysplasia, and adenocarcinoma did not have GERD symptoms.

Summary Background  Chronic watery diarrhoea is one of the most common symptoms prompting GI evaluation. Recently, new diagnostic considerations have emerged as possible factors in chronic diarrhoea. Aim  To review available data regarding diagnosis and treatment of chronic diarrhoea with an emphasis on bacterial overgrowth and bile acid malabsorption. Methods  A systematic search of the English language literature of chronic diarrhoea was performed focused on three possible aetiologies of diarrhoea: small intestinal bacterial overgrowth (SIBO), idiopathic bile salt malabsorption (IBAM), gluten responsive enteropathy. Results  Recent studies suggest that SIBO and bile acid malabsorption may have been underestimated as possible causes of chronic watery diarrhoea. Gluten intolerance with negative coeliac serology is a contentious possible cause of watery diarrhoea, but requires further research before acceptance as an entity. Conclusion  In patients with otherwise unexplained chronic watery diarrhoea, small intestinal bacterial overgrowth and bile salt malabsorption should be considered and investigated.