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Biomedical subjects

Michael D Jensen

Publications and source records attributed to Michael D Jensen.

At least 37 records · Page 2Linked to original sources
PubMed2005

Treatment of obesity with diet/exercise versus pioglitazone has distinct effects on lipoprotein particle size.

OBJECTIVE: We compared the effects of diet/exercise induce weight loss versus pioglitazone on lipoprotein particle characteristics in non-diabetic, insulin resistant adults to determine whether the responses and potential mechanisms for improvement are similar between these two insulin sensitizing regimens. METHODS AND RESULTS: Thirty-seven obese, insulin resistant volunteers were randomized to 19 weeks of either pioglitazone or diet/exercise treatment. Insulin sensitivity (Si) by IVGTT and lipoprotein subclass particle profiles by NMR was measured. Only diet/exercise lowered TG (-40+/-11 mg/dL), total (-29+/-4 mg/dL) and LDL cholesterol (-20+/-4 mg/dL; all p<0.01). Both diet/exercise and pioglitazone improved Si (p<0.05), decreased total LDL particles (-227+/-40 and -149+/-21 nmol/L, respectively, both p<0.001) and small LDL particles (-242+/-58 and -226+/-36, respectively, both p<0.001). Large LDL particle concentrations increased with both treatments. LDL particle subclasses changes correlated with changes in Si only in the diet/exercise group. CONCLUSION: In obese, insulin resistant non-diabetic adults, pioglitazone improved LDL particle characteristics in a manner similar to diet/exercise without changing TG, diabetic control, total or LDL cholesterol. This effect could have implications for atherosclerotic risk.

Adult↗
PubMed2005

Measuring VLDL-triglyceride turnover in humans using ex vivo-prepared VLDL tracer.

There has been more interest in VLDL-triglyceride (TG) kinetics during the last decade. Unfortunately, robust measurement methods are elaborate and not readily available. Here, we describe a method using unique, ex vivo labeling of the fatty acid moiety of VLDL-TG followed by intravenous bolus infusion in the same person. We found that plasma disappearance of ex vivo-labeled VLDL-TG was comparable to that of in vivo-labeled VLDL-TG and that turnover rates can be safely estimated from the log linear decay of VLDL-TG specific activity. We found minor labeling of the plasma FFA (oleate) pool, which was largely attributable to coinfusion of free [14C]triolein; VLDL-TG did not contribute substantially to the plasma FFA pool. The plasma decay curve of VLDL-TG was not affected by the presence of tracer in the FFA pool, provided that the data from 2 h after the VLDL tracer bolus infusion was used. The FFA contamination problem was circumvented by minor modification of the VLDL-TG tracer preparation. The approach we describe should expand the opportunity to study processes that cannot be assessed if the FFA precursor pool is labeled. This method for VLDL-TG tracer preparation can allow measurement of VLDL turnover, tissue uptake of VLDL-TG, and oxidation of VLDL-TG.

Adipose Tissue↗
PubMed2005

Neuroprotective mechanisms of curcumin against cerebral ischemia-induced neuronal apoptosis and behavioral deficits.

Increased oxidative stress has been regarded as an important underlying cause for neuronal damage induced by cerebral ischemia/reperfusion (I/R) injury. In recent years, there has been increasing interest in investigating polyphenols from botanical source for possible neuroprotective effects against neurodegenerative diseases. In this study, we investigated the mechanisms underlying the neuroprotective effects of curcumin, a potent polyphenol antioxidant enriched in tumeric. Global cerebral ischemia was induced in Mongolian gerbils by transient occlusion of the common carotid arteries. Histochemical analysis indicated extensive neuronal death together with increased reactive astrocytes and microglial cells in the hippocampal CA1 area at 4 days after I/R. These ischemic changes were preceded by a rapid increase in lipid peroxidation and followed by decrease in mitochondrial membrane potential, increased cytochrome c release, and subsequently caspase-3 activation and apoptosis. Administration of curcumin by i.p. injections (30 mg/kg body wt) or by supplementation to the AIN76 diet (2.0 g/kg diet) for 2 months significantly attenuated ischemia-induced neuronal death as well as glial activation. Curcumin administration also decreased lipid peroxidation, mitochondrial dysfunction, and the apoptotic indices. The biochemical changes resulting from curcumin also correlated well with its ability to ameliorate the changes in locomotor activity induced by I/R. Bioavailability study indicated a rapid increase in curcumin in plasma and brain within 1 hr after treatment. Together, these findings attribute the neuroprotective effect of curcumin against I/R-induced neuronal damage to its antioxidant capacity in reducing oxidative stress and the signaling cascade leading to apoptotic cell death.

Analysis of Variance↗
PubMed2005

Interindividual variation in posture allocation: possible role in human obesity.

Obesity occurs when energy intake exceeds energy expenditure. Humans expend energy through purposeful exercise and through changes in posture and movement that are associated with the routines of daily life [called nonexercise activity thermogenesis (NEAT)]. To examine NEAT's role in obesity, we recruited 10 lean and 10 mildly obese sedentary volunteers and measured their body postures and movements every half-second for 10 days. Obese individuals were seated, on average, 2 hours longer per day than lean individuals. Posture allocation did not change when the obese individuals lost weight or when lean individuals gained weight, suggesting that it is biologically determined. If obese individuals adopted the NEAT-enhanced behaviors of their lean counterparts, they might expend an additional 350 calories (kcal) per day.

Activities of Daily Living↗
PubMed2005

Phospholipase A2 in astrocytes: responses to oxidative stress, inflammation, and G protein-coupled receptor agonists.

Astrocytes comprise the major cell type in the central nervous system (CNS) and they are essential for support of neuronal functions by providing nutrients and regulating cell-to-cell communication. Astrocytes also are immune-like cells that become reactive in response to neuronal injury. Phospholipases A2 (PLA2) are a family of ubiquitous enzymes that degrade membrane phospholipids and produce lipid mediators for regulating cellular functions. Three major classes of PLA2 are expressed in astrocytes: group IV calcium-dependent cytosolic PLA2 (cPLA2), group VI calcium-independent PLA2 (iPLA2), and group II secretory PLA2(sPLA2). Upregulation of PLA2 in reactive astrocytes has been shown to occur in a number of neurodegenerative diseases, including stroke and Alzheimer's disease. This review focuses on describing the effects of oxidative stress, inflammation, and activation of G protein-coupled receptors on PLA2 activation, arachidonic acid (AA) release, and production of prostanoids in astrocytes.

Animals↗
PubMed2005

Action on obesity: report of a mayo clinic national summit.

In May 2004, representatives from local, state, and national public and private organizations met in Rochester, Minn, for the Action on Obesity Summit hosted by Mayo Clinic. The overall goal of this summit was to identify creative and effective strategies to Increase the US population's physical activity and improve nutrition to reverse the increasing prevalence of obesity. Ideas generated from selected abstract presentations and breakout sessions were prioritized and incorporated into an action model (available at www.actiononobesity.org) deemed feasible for implementation into most communities. Highlights of the presentations included a company that reported lower than expected health care expenditures secondary to a work site wellness program, a national initiative to increase physical activity (www.americaonthemove.org), and innovative work site nutritional strategies. The implementation model that emerged contained certain themes. Coordinated action at all levels will be required to substantially impact the increasing prevalence of obesity. Educational messages should be simple, consistent, tailored, and linked to benefits. Healthy food options in vending machines and restaurants and increased opportunities for daily physical activity should be available in schools, work sites, and communities. Legislative and policy changes should promote physical activity and improve nutrition. Support for research should be encouraged and outcome measures for interventions documented. A second Action on Obesity Summit is planned for June 9 and 10, 2005, that will review the progress made in the intervening year and continue to refine the implementation model to help address the obesity epidemic, one of the greatest public health problems facing the United States.

Humans↗
PubMed2004

Bariatric surgery: a systematic review and meta-analysis.

CONTEXT: About 5% of the US population is morbidly obese. This disease remains largely refractory to diet and drug therapy, but generally responds well to bariatric surgery. OBJECTIVE: To determine the impact of bariatric surgery on weight loss, operative mortality outcome, and 4 obesity comorbidities (diabetes, hyperlipidemia, hypertension, and obstructive sleep apnea). DATA SOURCES AND STUDY SELECTION: Electronic literature search of MEDLINE, Current Contents, and the Cochrane Library databases plus manual reference checks of all articles on bariatric surgery published in the English language between 1990 and 2003. Two levels of screening were used on 2738 citations. DATA EXTRACTION: A total of 136 fully extracted studies, which included 91 overlapping patient populations (kin studies), were included for a total of 22,094 patients. Nineteen percent of the patients were men and 72.6% were women, with a mean age of 39 years (range, 16-64 years). Sex was not reported for 1537 patients (8%). The baseline mean body mass index for 16 944 patients was 46.9 (range, 32.3-68.8). DATA SYNTHESIS: A random effects model was used in the meta-analysis. The mean (95% confidence interval) percentage of excess weight loss was 61.2% (58.1%-64.4%) for all patients; 47.5% (40.7%-54.2%) for patients who underwent gastric banding; 61.6% (56.7%-66.5%), gastric bypass; 68.2% (61.5%-74.8%), gastroplasty; and 70.1% (66.3%-73.9%), biliopancreatic diversion or duodenal switch. Operative mortality (< or =30 days) in the extracted studies was 0.1% for the purely restrictive procedures, 0.5% for gastric bypass, and 1.1% for biliopancreatic diversion or duodenal switch. Diabetes was completely resolved in 76.8% of patients and resolved or improved in 86.0%. Hyperlipidemia improved in 70% or more of patients. Hypertension was resolved in 61.7% of patients and resolved or improved in 78.5%. Obstructive sleep apnea was resolved in 85.7% of patients and was resolved or improved in 83.6% of patients. CONCLUSIONS: Effective weight loss was achieved in morbidly obese patients after undergoing bariatric surgery. A substantial majority of patients with diabetes, hyperlipidemia, hypertension, and obstructive sleep apnea experienced complete resolution or improvement.

Adolescent↗
PubMed2004

Abundance of two human preadipocyte subtypes with distinct capacities for replication, adipogenesis, and apoptosis varies among fat depots.

Fat depots vary in function and size. The preadipocytes that fat cells develop from exhibit distinct regional characteristics that persist in culture. Human abdominal subcutaneous cultured preadipocytes undergo more extensive lipid accumulation, higher adipogenic transcription factor expression, and less TNF-alpha-induced apoptosis than omental preadipocytes. We found higher replicative potential in subcutaneous and mesenteric than in omental preadipocytes. In studies of colonies arising from single preadipocytes, two preadipocyte subtypes were found, one capable of more extensive replication, differentiation, and adipogenic transcription factor expression and less apoptosis in response to TNF-alpha than the other. The former was more abundant in subcutaneous and mesenteric than in omental preadipocyte populations, potentially contributing to regional variation in replication, differentiation, and apoptosis. Both subtypes were found in strains derived from single human preadipocytes stably expressing telomerase, confirming that both subtypes are of preadipocyte lineage. After subcloning of cells of either subtype, both subtypes were found, indicating that switching can occur between subtypes. Thus proportions of preadipocyte subtypes with distinct cell-dynamic properties vary among depots, potentially permitting tissue plasticity through subtype selection during development. Furthermore, mesenteric preadipocyte cell-dynamic characteristics are distinct from omental cells, indicating that visceral fat depots are not functionally uniform.

Adipocytes↗
PubMed2004

Vascular response to angiotensin II in upper body obesity.

Upper body obesity is associated with insulin resistance, hypertension, and endothelial dysfunction. We examined forearm vascular function in response to vasodilator (endothelium-dependent and endothelium-independent) and vasoconstrictor stimuli in 8 normotensive, upper body/viscerally obese men with a positive family history of hypertension and 8 age-matched nonobese men. We also measured body composition and insulin regulation of free fatty acid (FFA) and glucose metabolism. Forearm blood flow was measured before and during brachial artery infusions of acetylcholine (Ach), sodium nitroprusside (NTP), and angiotensin II (+/-nitric oxide synthase [NO]) synthase blockade with N(G)-monomethyl L-arginine [L-NMMA]). On a separate day, baseline and insulin-regulated glucose ([3-3H]glucose) and FFA ([9,10-3H]palmitate) turnover were measured. The vasoconstrictor response to angiotensin II was greater (P<0.05) in obese men than in nonobese men, whereas endothelium-dependent vasodilation was similar. The slope of the angiotensin II dose-response curve correlated significantly with the basal plasma palmitate concentration. Basal and insulin-mediated glucose disposal was significantly reduced and FFA turnover significantly increased in viscerally obese men. No differences in endothelium-independent vasodilation or relationships between vascular responsivity and palmitate and glucose kinetics or body composition were found. Angiotensin II-stimulated forearm vasoconstriction is increased in viscerally obese normotensive men.

Acetylcholine↗
PubMed2004

Measuring committed preadipocytes in human adipose tissue from severely obese patients by using adipocyte fatty acid binding protein.

To understand the significance of the reported depot differences in preadipocyte dynamics, we developed a procedure to identify committed preadipocytes in the stromovascular fraction of fresh human adipose tissue. We documented that adipocyte fatty acid binding protein (aP2) is expressed in human preadipocyte clones capable of replication, indicating that can be used as a marker of committed preadipocytes. Because aP2 expression can be induced in macrophages, stromovascular cells were also stained for the macrophage marker CD68. We found aP2+CD68- cells (designated as committed preadipocytes) that did not have lipid droplets (true preadipocytes) and that did have lipid droplets < 6.5 microm in diameter (very immature adipocytes). Adipose tissue from subcutaneous, omental, and mesenteric depots was obtained from nine patients undergoing bariatric surgery for measurement of stromovascular cell number, the number of committed preadipocytes (aP2+CD68-), aP2+ macrophages (aP2+CD68+), and aP2- macrophages (aP2-CD68+). The number of committed preadipocytes did not differ significantly between depots but varied >20-fold among individuals. Total cell number, stromovascular cell number, and the number of aP2- macrophages was less (P < 0.05) in subcutaneous than in omental fat (means +/- SE, in millions: subcutaneous, 2.3 +/- 0.3, 1.4 +/- 0.3, and 0.17 +/- 0.08; and omental, 4.8 +/- 0.7, 3.8 +/- 0.5, and 0.34 +/- 0.06); mesenteric depot was intermediate. These data indicate that the cellular composition of adipose tissue varies between depots and between individuals. The ability to quantify committed preadipocytes in fresh adipose tissue should facilitate study of adipose tissue biology.

Adipocytes↗
PubMed2004

Leptin, insulin resistance, and liver fibrosis in human nonalcoholic fatty liver disease.

BACKGROUND/AIMS: Data from animal models of fibrosis and fatty liver suggest that leptin may mediate the profibrogenic responses in the liver, but the association of leptin and liver fibrosis in human nonalcoholic fatty liver disease (NAFLD) remains undefined. We aimed at determining the relation between leptin and liver fibrosis in human NAFLD. METHODS: Human plasma leptin and several indicators of insulin resistance were measured in 88 NAFLD patients and matched controls. RESULTS: Leptin levels were significantly greater in patients with more advanced fibrosis (P = 0.005). By multivariate analysis, the significant association between leptin and fibrosis was abolished (adjusted P = 0.3) when controlling for confounders including age, gender, BMI, diabetes and insulin resistance. Only age (adjusted P = 0.006) and insulin sensitivity (adjusted P = 0.04) correlated significantly with fibrosis stage. A second liver biopsy was performed in 39 out of the 88 patients at 27.9 +/- 16 months. Leptin levels were not significantly different between patients who had fibrosis progression (n = 10) and those who did not (n = 29). CONCLUSIONS: In human NAFLD, no relationship between leptin levels and fibrosis stage was demonstrated. The correlation of leptin and fibrosis severity seems to be an indicator of the factors that determine leptin production.

Adult↗
PubMed2004

Insulin regulation of free fatty acid kinetics in adult cystic fibrosis patients with impaired glucose tolerance.

Cystic fibrosis (CF) patients are insulin-resistant with regards to suppression of hepatic glucose production and proteolysis, but the effect of insulin on adipose free fatty acid (FFA) release has not been studied. [9,10-(3)H]palmitate kinetics were measured in 11 stable adult CF patients with impaired glucose tolerance (IGT) and 9 normal control subjects. Baseline plasma palmitate concentrations [CF = 99 +/- 13 (median 74, range 65 to 187); control = 88 +/- 9 (88, 46 to 138) micromol/L, P = .9] and palmitate flux [CF = 114 +/- 11 (100, 72 to 171); control = 105 +/- 12 (106, 54 to 182) micromol/min, P = 0.9] were not different between CF patients and controls. During a euglycemic clamp with infusion of insulin to physiologic postprandial levels, however, palmitate concentrations tended to be higher in CF patients: CF = 18 +/- 3 (13, 10 to 47), control = 12 +/- 1 (11, 8 to 18) micromol/L, P = 0.08. The higher palmitate concentrations during hyperinsulinemia appeared to be due to reduced suppression of adipose tissue palmitate release, because mean palmitate flux was 33% greater in CF subjects [32 +/- 5 (26, 17 to 66) micromol/min] than controls: [24 +/- 2 (23, 17 to 34) micromol/min], P = .20. There was considerably greater heterogeneity in insulin-induced suppression of plasma palmitate concentration and flux in CF patients compared to normal control subjects. In summary, a defect in insulin suppression of lipolysis was seen in clinically stable CF patients with IGT, similar to what has been described in CF for amino acid and glucose metabolism. This quantitative difference in lipolysis may account for inadequate insulin-induced suppression of hepatic glucose production in CF, and may be a metabolic adaptation to increased energy needs.

Adipose Tissue↗
PubMed2004

Preventing overestimation of pixels in computed tomography assessment of visceral fat.

OBJECTIVE: Computed tomography (CT) is a common research procedure for measuring abdominal fat distribution, but little is written about the software used to analyze images. Our objective was to compare in-house and commercially available software for quantitative measurement of abdominal fat distribution. In the process, we encountered some unexpected problems. RESEARCH METHODS AND PROCEDURES: A total of 123 volunteers had single-slice abdominal CT images taken that were used to evaluate various aspects of the commercial image analysis program. RESULTS: The agreement between the commercial and in-house programs was excellent (r = 0.996, p < 0.00,001) for both total and intraabdominal fat, and we were able to reduce between-observer variability in measured fat areas through the use of statistical handling of region of interest information. We also noted that intracolonic contents sometimes had the same Hounsfield units as adipose tissue. We analyzed single-slice CT images from 50 volunteers to determine the potential impact of this effect on visceral fat area; the overestimate of visceral fat area was 19 +/- 22% (maximum, 112% overestimate). The commercial program could prevent this error, whereas our in-house program could not. DISCUSSION: We concluded that a readily available commercial image analysis program compares well with a previously validated in-house program and that it offers some advantages with respect to preventing overestimation of pixels as visceral fat.

Abdomen↗
PubMed2004

Splanchnic lipolysis in human obesity.

Elevated FFA concentrations have been shown to reproduce some of the metabolic abnormalities of obesity. It has been hypothesized that visceral adipose tissue lipolysis releases excess FFAs into the portal vein, exposing the liver to higher FFA concentrations. We used isotope dilution/hepatic vein catheterization techniques to examine whether intra-abdominal fat contributes a greater portion of hepatic FFA delivery in visceral obesity. Obese women (n = 24) and men (n = 20) with a range of obesity phenotypes, taken together with healthy, lean women (n = 12) and men (n = 12), were studied. Systemic, splanchnic, and leg FFA kinetics were measured. The results showed that plasma FFA concentrations were approximately 20% greater in obese men and obese women. The contribution of splanchnic lipolysis to hepatic FFA delivery ranged from less than 10% to almost 50% and increased as a function of visceral fat in women (r = 0.49, P = 0.002) and in men (r = 0.52, P = 0.002); the slope of the relationship was greater in women than in men (P < 0.05). Leg and splanchnic tissues contributed a greater portion of systemic FFA release in obese men and women than in lean men and women. We conclude that the contribution of visceral adipose tissue lipolysis to hepatic FFA delivery increases with increasing visceral fat in humans and that this effect is greater in women than in men.

Abdomen↗
PubMed2004

Evidence of increased visceral obesity and reduced physical fitness in healthy insulin-resistant first-degree relatives of type 2 diabetic patients.

OBJECTIVE: First-degree relatives (FDR) of type 2 diabetic patients are often insulin resistant. Visceral obesity is closely linked to both insulin resistance and type 2 diabetes. We therefore hypothesized that the inheritance of an increased tendency to store fat in visceral fat depots may be a characteristic phenotypic feature in FDR contributing to their insulin resistance. DESIGN AND METHODS: We measured fat distribution in 20 FDR and 14 age-, gender- and body mass index (BMI)-matched controls employing dual energy X-ray absorbtiometry (DEXA)- and computed tomography (CT)-scanning. Insulin-stimulated glucose uptake (ISGU) was determined by a hyperinsulinemic clamp and maximal aerobic work capacity (VO2 max) by a bicycle ergometer test. Baseline lipolysis was measured using [3H]palmitate. The activity level of the hypothalamic-pituitary-adrenal axis was assessed as the 24 h urinary (u)-cortisol/creatinine ratio. RESULTS: All subjects had a normal oral glucose tolerance test (OGTT), but FDR were insulin resistant (ISGU: 6.64+/-0.48 vs 9.12+/-0.98 mg/kg ffm/min, P=0.01). Despite similar BMI (25.2+/-0.5 vs 24.8+/-0.7 kg/m2, P=0.61) and overall fat mass (26.4+/-1.6 vs 24.2+/-2.1%, P=0.41) in FDR vs controls, the amount of visceral adipose tissue was substantially increased (65.9+/-10.0 vs 40.1+/-11.3 cm2, P<0.05) and VO2 max was reduced (52.2+/-3.1 vs 63.3+/-3.9 ml/kg ffm/min, P<0.05) in FDR. Visceral adiposity was inversely correlated with ISGU (FDR: r=-0.52, P<0.05; controls: r=-0.65, P<0.01) and in multiple regression analysis visceral adiposity (P<0.01), VO2 max (P<0.001) and a family history of type 2 diabetes (P<0.05) (r2=0.64) all significantly and independently contributed to the level of ISGU. Baseline palmitate appearance (145+/-10 vs 139+/-15 micromol/min, P=0.74) and the 24 h u-cortisol/creatinine ratio ((24.9+/-1.3 vs 27.4+/-2.0).10(-6), P=0.28) were both comparable in the two groups. CONCLUSION: Healthy but insulin-resistant FDR have enhanced visceral obesity and reduced VO2 max compared with people without a family history of diabetes, despite similar BMI and overall fat mass. Both the visceral adiposity and reduced aerobic fitness are strongly associated with and may contribute to their insulin resistance.

Adipose Tissue↗
PubMed2004

Bariatric surgery. For the right patient, procedure can be effective.

Obesity is a chronic health problem with associated medical complications involving multiple physiologic systems. Some obese patients succeed in losing weight with traditional, nonsurgical therapies and interventions. In this article, Drs Mattison and Jensen discuss the option of bariatric surgery for those patients who have not responded to medically sound weight-loss programs and for whom the complications of obesity pose a high and ongoing risk.

Body Mass Index↗
PubMed2003

Phospholipase A2 in the central nervous system: implications for neurodegenerative diseases.

Phospholipase A2 (PLA2) belongs to a family of enzymes that catalyze the cleavage of fatty acids from the sn-2 position of phospholipids. There are more than 19 different isoforms of PLA2 in the mammalian system, but recent studies have focused on three major groups, namely, the group IV cytosolic PLA2, the group II secretory PLA2 (sPLA2), and the group VI Ca(2+)-independent PLA2. These PLA2s are involved in a complex network of signaling pathways that link receptor agonists, oxidative agents, and proinflammatory cytokines to the release of arachidonic acid (AA) and the synthesis of eicosanoids. PLA2s acting on membrane phospholipids have been implicated in intracellular membrane trafficking, differentiation, proliferation, and apoptotic processes. All major groups of PLA2 are present in the central nervous system (CNS). Therefore, this review is focused on PLA2 and AA release in neural cells, especially in astrocytes and neurons. In addition, because many neurodegenerative diseases are associated with increased oxidative and inflammatory responses, an attempt was made to include studies on PLA2 in cerebral ischemia, Alzheimer's disease, and neuronal injury due to excitotoxic agents. Information from these studies has provided clear evidence for the important role of PLA2 in regulating physiological and pathological functions in the CNS.

Alzheimer Disease↗