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Biomedical subjects

N V Dhurandhar

Publications and source records attributed to N V Dhurandhar.

At least 19 recordsLinked to original sources
PubMed2006

Comparison of combinations of drugs for treatment of obesity: body weight and echocardiographic status.

BACKGROUND: Obesity treatment with single drugs produces weight losses of about 8-10% of initial body weight. Few studies of combinations of drugs for treating obesity have been published. The combination of phentermine, an adrenergic agent, and fenfluramine, a serotonergic agent, (phen-fen) produced weight losses of about 15% of initial body weight. Fenfluramine is no longer available because it was associated with cardiac valve lesions. Phentermine-fluoxetine (phen-flu) has been proposed as an alternative for phen-fen. OBJECTIVE: To compare the efficacy of treatment and prevalence of cardiac valve abnormalities on phen-flu vs phen-fen. DESIGN: Retrospective chart review of all patients treated for at least 3 months with phen-flu (N=97) to a random sample of patients treated with phen-fen (N=98) in the Clinical Nutrition Clinic at the University of Wisconsin. Comparison of echocardiograms in all patients treated solely with phen-flu (N=21) to a random sample of patients treated with phen-fen (N=47), and to a group of subjects never treated with obesity drugs (N=26). RESULTS: With last observation carried forward analysis (LOCF), at 6 months of treatment the phen-fen patients lost 12.6+/-0.6% of baseline weight and phen-flu patients lost 9.0+/-0.6% (P<0.001). With completers analysis, there were no significant differences in weight loss as a percent of baseline weight at 6 months (14.4+/-0.6 vs 13.3+/-0.9%). LOCF decreases in body mass index (BMI) at 6 months were -5.3 and -3.6 kg/m(2) for phen-fen and phen-flu, respectively (P<0.001), and 6.2+/-0.3 vs 5.4+/-0.4 kg/m(2), respectively, for the completers analysis (P - NS). Dropout rate at 6 months was higher in phen-flu subjects (44 vs 28%). In subjects without atherosclerosis of valves (presumably pre-existing), cardiac valve lesions occurred in eight of 38 phen-fen subjects and in none of 15 phen-flu subjects or 25 control subjects who had not been treated with drugs. CONCLUSIONS: The combination of phentermine and fluoxetine was not as effective as phen-fen, but was not associated with cardiac valve lesions. Longer term, larger scale studies of phen-flu are warranted.

Adult↗
PubMed2006

Putative contributors to the secular increase in obesity: exploring the roads less traveled.

OBJECTIVE: To investigate plausible contributors to the obesity epidemic beyond the two most commonly suggested factors, reduced physical activity and food marketing practices. DESIGN: A narrative review of data and published materials that provide evidence of the role of additional putative factors in contributing to the increasing prevalence of obesity. DATA: Information was drawn from ecological and epidemiological studies of humans, animal studies and studies addressing physiological mechanisms, when available. RESULTS: For at least 10 putative additional explanations for the increased prevalence of obesity over the recent decades, we found supportive (although not conclusive) evidence that in many cases is as compelling as the evidence for more commonly discussed putative explanations. CONCLUSION: Undue attention has been devoted to reduced physical activity and food marketing practices as postulated causes for increases in the prevalence of obesity, leading to neglect of other plausible mechanisms and well-intentioned, but potentially ill-founded proposals for reducing obesity rates.

Age Factors↗
PubMed2006

Adipogenic human adenovirus-36 reduces leptin expression and secretion and increases glucose uptake by fat cells.

OBJECTIVE: Human adenovirus Ad-36 causes adiposity in animal models and enhances differentiation and lipid accumulation in human and 3T3-L1 preadipocytes, which may, in part, explain the adipogenic effect of Ad-36. We determined the consequences of Ad-36 infection on leptin and glucose metabolism in fat cells. DESIGN: 3T3-L1 preadipocytes were used to determine the effect of infection by human adenoviruses Ad-36, Ad-2, Ad-9 and Ad-37 on leptin secretion and lipid accumulation. Rat primary adipocytes were used to determine the effect of Ad-36 infection on leptin secretion and glucose uptake in vitro. Furthermore, the effect of Ad-36 on expressions of leptin and selected genes of de novo lipogenesis pathway of visceral adipose tissue were compared ex vivo, between Ad-36 infected and uninfected control rats. RESULTS: Ad-36 suppressed the expression of leptin mRNA in 3T3-L1 cells by approximately 58 and 52% on days 3 and 5 post-infection, respectively. Leptin release normalized to cellular lipid content was 51% lower (P<0.002) in the Ad-36 infected 3T3-L1 cells. Lipid accumulation was significantly greater and leptin secretion was lower for the 3T3-L1 cells infected with other human adenoviruses Ad-9, Ad-36, or Ad-37. Whereas, human adenovirus Ad-2 did not influence cellular lipid accumulation or the leptin release. In rat primary adipocytes, Ad-36 reduced leptin release by about 40% in presence of 0.48 (P<0.01) or 1.6 nM insulin (P<0.05) and increased glucose uptake by 93% (P<0.001) or 18% (P<0.05) in presence of 0 or 0.48 nM insulin, respectively. Next, the adipose tissue of Ad-36 infected rats showed two to fivefold lower leptin mRNA expression, and 1.6- to 21-fold greater expressions for acetyl Co-A carboxylase-1 and 1.2- to 6.3-fold greater expressions for fatty acid synthase, key genes of de novo lipogenesis, compared to the uninfected weight and adiposity matched controls. CONCLUSION: The in vitro and ex vivo studies show that Ad-36 modulates adipocyte differentiation, leptin production and glucose metabolism. Whether such a modulation contributes to enhanced adipogenesis and consequent adiposity in Ad-36 infected animals or humans needs to be determined.

3T3-L1 Cells↗
PubMed2006

Viral mRNA expression but not DNA replication is required for lipogenic effect of human adenovirus Ad-36 in preadipocytes.

OBJECTIVE: Human adenovirus Ad-36 causes adiposity in animal models and shows association with human obesity. Ad-36 enhances differentiation of 3T3-L1 and human preadipocytes, without cell lysis, a characteristic that may contribute to its adipogenic effect observed in vivo. Ad-2, another human adenovirus is nonadipogenic in animals and in 3T3-L1 cells and shows no correlation with human obesity. The objective of this study was to determine the adipogenic roles of viral mRNA and DNA, which may explain the differential effects of Ad-36 and Ad-2 on preadipocyte differentiation. METHODS: This study determined the duration of selected Ad-36 gene expression in 3T3-L1 cells, and the effect on preadipocytes differentiation, when Ad-36 gene expression was attenuated by Cidofovir, an antiadenoviral agent. RESULTS: The results showed that Ad-36, but not Ad-2, expresses viral mRNA. Ad-36 gene expression peaked at 2-4 days postinoculation and very low levels persisted after day 7. Despite the viral mRNA expression, Ad-36 infection of 3T3-L1 cells was abortive as indicated by a progressive decrease in viral DNA quantity. Attenuation of Ad-36 mRNA expression by Cidofovir reduced the adipogenic effect of the virus. CONCLUSION: In conclusion, viral mRNA expression, although transient, is a prerequisite for enhancing differentiation of preadipocytes by Ad-36. Viral DNA replication was not required for the effect. This is the first evidence for the role of gene expression of an adipogenic human virus in enhancing preadipocytes differentiation. This study provides the basis for further understanding novel regulatory modulators of preadipocytes differentiation.

3T3-L1 Cells↗
PubMed2005

Human adenovirus-36 is associated with increased body weight and paradoxical reduction of serum lipids.

BACKGROUND: Human adenovirus-36 (Ad-36) increases adiposity and paradoxically lowers serum cholesterol and triglycerides in chickens, mice, and non-human primates. The role of Ad-36 in human obesity is unknown. OBJECTIVES: To determine the prevalence of Ad-36 antibodies in obese and nonobese humans. To evaluate the association of Ad-36 antibodies with body mass index (BMI) and serum lipids. DESIGN: Cohort study. Volunteers from obesity treatment programs, communities, and a research study. SUBJECTS: Obese and nonobese volunteers at the University of Wisconsin, Madison, WI, and the Bowen Center, Naples, Florida. Obese and thin volunteer research subjects and 89 twin pairs at Columbia University, New York. INTERVENTIONS: Study 1: 502 subjects; serum neutralization assay for antibodies to Ad-2, Ad-31, Ad-36, and Ad-37; serum cholesterol and triglycerides assays. Study 2: BMI and %body fat in 28 twin pairs discordant for Ad-36 antibodies. MAIN OUTCOME MEASURES: Presence of antibodies to adenoviruses, BMI, serum cholesterol and triglycerides levels. RESULTS: Significant (P < 0.001) association of obesity and positive Ad-36 antibody status, independent of age, sex, and collection site. Ad-36 antibodies in 30% of obese, 11% of nonobese. Lower serum cholesterol and triglycerides (P < 0.003) in Ad-36 antibody-positive vs -negative subjects. Twin pairs: antibody-positive twins had higher BMIs (24.5+/-5.2 vs 23.1+/-4.5 kg/m2, P < 0.03) and %body fat (29.6+/-9.5% vs 27.5+/-9.9%, P < 0.04). No association of Ad-2, Ad-31, or Ad-37 antibodies with BMI or serum lipids. CONCLUSIONS: Ad-36 is associated with increased body weight and lower serum lipids in humans. Prospective studies are indicated to determine if Ad-36 plays a role in the etiology of human obesity.

Adenovirus Infections, Human↗
PubMed2004

Novel short-term effects of adenovirus Ad-36 on hamster lipoproteins.

OBJECTIVE: Human adenovirus Ad-36 induces adiposity and lowers total serum cholesterol in chickens, mice and marmosets and Ad-36 antibodies are associated with human obesity. We examined the early effects of Ad-36 inoculation on plasma cholesterol levels in hamsters fed a hyperlipidemic diet. DESIGN: A total of 32 male Golden Syrian hamsters were divided into two equal weight-matched groups and intranasally inoculated with Ad-36 (INF: infected) or media (CON: control). In each group, the animals were fed either a purified diet (PF, n=8) 40%en fat +/-194 mg cholesterol/1000 kcal or chow (C, n=8) ad libitum. Animals were killed 5 weeks postinoculation. RESULTS: Nested PCR assay detected Ad-36 DNA in the lung, liver, visceral adipose tissue and skeletal muscle of the INF group, but not in the CON animals. Ad-36 antibodies were detected in the INF group only. For all animals, total plasma cholesterol (TC) was not significantly affected by Ad-36 treatment (203+/-92 vs 193+/-75 mg/dl, P=NS; INF vs CON, respectively). In 5 weeks, Ad-36 infection had no effect on TC concentration in hamsters fed chow (128+/-39 vs 130+/-27 mg/dl, INF-C vs CON-C, respectively) or those fed PF (269+/-70 vs 256+/-47 mg/dl, INF-P vs CON-P, respectively). However, lipoproteins isolated by density gradient ultracentrifugation showed a greater proportion of LDL cholesterol in INF animals, as compared to CON (28.4+/-1.6% vs 16.4+/-1.2%, P=0.02), regardless of dietary treatment (INF-P vs CON-P: 27.3+/-2.1 vs 15.7+/-1.5%, P=0.07; and INF-C vs CON-C: 29.4+/-1.2 vs 17.0+/-1.1%, P=0.009). This shift appears to be from HDL cholesterol to the LDL fractions. CONCLUSION: These data suggest that in the hamster (a model resembling several aspects of human lipoprotein metabolism), Ad-36 infection may acutely affect the intravascular processing of lipoproteins resulting in a more atherogenic lipoprotein profile.

Adenoviridae Infections↗
PubMed2001

Transmissibility of adenovirus-induced adiposity in a chicken model.

BACKGROUND: We previously reported that human adenovirus Ad-36 induces adiposity and paradoxically lower levels of serum cholesterol (CHOL) and triglycerides (TG) in animals. OBJECTIVE: To evaluate the transmissibility of Ad-36 and Ad-36 induced adiposity using a chicken model. DESIGN: Experiment 1--four chickens were housed (two per cage) and one from each cage was inoculated with Ad-36. Duration of presence of Ad-36 DNA in the blood of all chickens was monitored. Experiment 2--two groups of chickens were intranasally inoculated with Ad-36 (infected donors, I-D) or media (control donors, C-D). Blood drawn 36 h later from I-D and C-D groups was inoculated into wing veins of recipient chickens (infected receivers, I-R, and control receivers, C-R, respectively). On sacrifice, 5 weeks post-inoculation, blood was drawn, body weight noted and visceral fat was separated and weighed. RESULTS: Experiment 1--Ad-36 DNA appeared in the blood of the inoculated chickens and that of uninoculated chickens (cage mates) within 12 h of inoculation and the viral DNA persisted up to 25 days in the blood. Experiment 2--compared with C-D, visceral and total body fat were significantly greater and CHOL significantly lower for the I-D and I-R. TG were significantly lower for the I-D. Ad-36 was isolated from 12 out of 16 blood samples of the I-D that were used for inoculating I-R chickens. Ad-36 DNA was present in the blood and the adipose tissue of the I-D and I-R but not in the skeletal muscles of animals selected randomly for testing. CONCLUSION: As seen in experiment 1, Ad-36 infection can be transmitted horizontally from an infected chicken to another chicken sharing the cage. Additionally, experiment 2 demonstrated blood-borne transmission of Ad-36-induced adiposity in chickens. Transmissibility of Ad-36-induced adiposity in chicken model raises serious concerns about such a possibility in humans that needs further investigation.

Adenovirus Infections, Human↗
PubMed2001

Infectobesity: obesity of infectious origin.

In the U.S., the prevalence of obesity increased by 30% from 1980 to 1990, and this increase appears to be continuing. Although obesity has multiple etiologies, an overlooked possibility is obesity of an infectious origin. Six pathogens are reported to cause obesity in animals. Canine distemper virus was the first virus reported to cause obesity in mice, followed by Rous-associated virus-7, an avian retrovirus, which has been shown to cause stunting, obesity and hyperlipidemia in chickens. Next, the obesity-promoting effect of Borna disease virus was demonstrated in rats. Scrapie agents were reported to induce obesity in mice and hamsters. The final two reports were of SMAM-1, an avian adenovirus, and Ad-36, a human adenovirus that caused obesity in animals. Additionally, an association with human obesity is the unique feature of SMAM-1 and Ad-36. Although the exact mechanism of pathogen-induced obesity is unclear, infection attributable to certain organisms should be included in the long list of potential etiological factors for obesity. In addition, the involvement of some pathogens in etiology of obesity suggests the possibility of a similar role for additional pathogens.

Animals↗
PubMed2000

Direct quantification of AD-36 adenovirus DNA by capillary electrophoresis with laser-induced fluorescence.

An adenovirus, AD-36, has been linked to human adiposity and a sensitive and reliable quantitative method is required to assess AD-36 viral loads. This report describes direct detection of AD-36 viral DNA, which is the first method to quantitate DNA without amplification. Total genomic DNA is hybridized with an AD-36 specific fluorescently labeled probe and analyzed by capillary electrophoresis with laser-induced fluorescence. The minimum detectable quantity is 10.3 ng/ml, corresponding to 282 copies of AD-36 with a precision of 1-6%. These results indicate that direct detection with capillary electrophoresis with laser-induced fluorescence (CE-LIF) is a reliable and sensitive method for quantifying AD-36 viral DNA.

Adenoviridae↗
PubMed2000

Increased adiposity in animals due to a human virus.

BACKGROUND: Four animal models of virus-induced obesity including adiposity induced by an avian adenovirus have been described previously. This is the first report of adiposity induced in animals by a human virus. OBJECTIVE: We investigated the adiposity promoting effect of a human adenovirus (Ad-36) in two different animal models. DESIGN: Due to the novel nature of the findings we replicated the experiments using a chicken model three times and a mammal model once. In four separate experiments, chickens and mice were inoculated with human adenovirus Ad-36. Weight matched groups inoculated with tissue culture media were used as non-infected controls in each experiment. Ad-36 inoculated and uninfected control groups were housed in separate rooms under biosafety level 2 or better containment. The first experiment included an additional weight matched group of chickens that was inoculated with CELO (chick embryo lethal orphan virus), an avian adenovirus. Food intakes and body weights were measured weekly. At the time of sacrifice blood was drawn and visceral fat was carefully separated and weighed. Total body fat was determined by chemical extraction of carcass fat. RESULTS: Animals inoculated with Ad-36 developed a syndrome of increased adipose tissue and paradoxically low levels of serum cholesterol and triglycerides. This syndrome was not seen in chickens inoculated with CELO virus. Sections of the brain and hypothalamus of Ad-36 inoculated animals did not show any overt histopathological changes. Ad-36 DNA could be detected in adipose tissue, but not skeletal muscles of randomly selected animals for as long as 16 weeks after Ad-36 inoculation. CONCLUSIONS: Data from these animal models suggest that the role of viral disease in the etiology of human obesity must be considered.

Adenovirus Infections, Human↗
PubMed1999

Initial weight loss as a predictor of response to obesity drugs.

BACKGROUND: Initial weight loss has been used as a predictor of long-term response to obesity drugs. Discontinuation of drugs has been recommended if weight loss is not > or =1.81 kg (4 lb) in the first month of treatment. OBJECTIVE: We compared the weight loss response at 6 months of patients losing > or =1.81 kg (responders) vs. < 1.81 kg (non-responders) in the first month of treatment with the combination of fenfluramine and phentermine. DESIGN: Outcomes at 6 months in 975 patients treated in a comprehensive program of phentermine (15-30 mg/d) d,l-fenfluramine (20-60 mg/d), were compared for responders vs. non-responders. RESULTS: In the total population, first month weight loss highly correlated with % reduction in body mass index (BMI) after 6 months of treatment (P<0.001). The reduction in baseline BMI after 6 months treatment was greater for the responders (15.9% vs. 10%, P<0.02). However, the North American Association for the Study of Obesity (NAASO) guidelines for drug treatment of obesity state that a 5% weight loss produces significant health benefits, and may be used as a criteria for success. At 6 months, 76%, 37% and 14% of the non-respondents had lost > or = 5%, > or = 10% and > or = 15% of baseline BMI, respectively. After 6 months treatment the reductions in serum cholesterol, triglycerides and LDL-cholesterol were 0.55, 0.31 and 0.42 mmol/L, respectively, (P< or =0.006), for the non-responders. Adverse effects after 6 months of treatment and the dropout rates after 1 y of treatment were not significantly different for the two groups. CONCLUSIONS: Although, the first month weight loss predicted the long-term response to phen-fen treatment, it was inadequate in identifying the non-responders and may unnecessarily preclude potential beneficiaries of the treatment.

Adult↗
PubMed1999

8th Annual International Conference on Obesity and Non-Insulin Dependent Diabetes Mellitus: novel drug developments.

The 8th Obesity & Non-Insulin Dependent Diabetes Mellitus and Novel Drug Developments Conference organised by International Business Communication, Inc. was held on 19th - 20th, April 1999 in London, followed by an one-day symposium on Novel Drug Developments for NIDDM & Insulin Resistance. More than 100 delegates from both academic and industrial institutes attended the two meetings. The presentations provided insights into the understanding of mechanisms and developments of novel drugs for treatments of obesity and Type 2 diabetes. This review offers a general overview of the fields in appetite suppression, thermogenesis and insulin sensitisation. Discussions focused on several emerging therapeutic areas, including novel compound developments and target identification of receptors, proteins and viruses with the use of conventional methods and recently emerged technologies, such as bioinformatics and invertebrate modelling of human systems.

Journal Article↗
PubMed1997

Long-term drug treatment of obesity in a private practice setting.

This study evaluated the long-term efficacy and safety of the combination of phentermine and fenfluramine for the treatment of obesity in a private practice setting. A total of 1388 consecutive, qualified patients presenting to a private general internal medicine practice in Charlotte, NC, were enrolled with eligibility criteria including: age 18 years to 60 years, 20% over "desirable" bodyweight or body mass index > 27, no serious medical or psychiatric disease, and no contraindications to drug therapy. Patients were instructed in diet, exercise, and behavior modification techniques and received phentermine (15 mg/day to 30 mg/day) and fenfluramine (20 mg/day to 60 mg/day) continuously for over 3 years. Average duration of treatment was 15.9 months, and average weight loss at the last visit was 11.6 kg, or 11.7% of initial bodyweight. For patients completing 1 year of drug treatment, mean weight loss was 16.5 kg, or 16% of initial weight. Weight loss persisted for 2 years, but partial regain was seen at 3 years. The dropout rates were 18% at 6 months, 39% at 1 year, 68% at 2 years, and 78% at 3 years. At 1 year, blood pressure of hypertensive patients fell from 151/95 mm Hg to 127/78 mm Hg, and serum cholesterol and triglycerides of hyperlipidemic patient fell by 0.750 mmol/L (29 mg/dL) and 0.937 mmol/L (83 mg/dL), respectively. Adverse events were modest. We conclude that, in a private practice setting, long-term treatment of obesity with the combination of phentermine, fenfluramine, and a weight maintenance program is generally safe and effective. More research is needed to determine efficacy and safety for longer than 3 years.

Adolescent↗
PubMed1997

Association of adenovirus infection with human obesity.

We previously reported that chickens infected with the avian adenovirus SMAM-1 developed a unique syndrome characterized by excessive intra-abdominal fat deposition accompanied by paradoxically low serum cholesterol and triglyceride levels. There have been no previous reports of avian adenoviruses infecting humans. We screened the serum of 52 humans with obesity in Bombay, India, for antibodies against SMAM-1 virus using the agar gel precipitation test (AGPT) method. Bodyweights and serum cholesterol and triglyceride levels were compared in SMAM-1-positive (P-AGPT) and SMAM-1-negative (N-AGPT) groups. Ten subjects were positive for antibodies to SMAM-1, and 42 subjects did not have antibodies. The P-AGPT group had a significantly higher bodyweight (p < 0.02) and body mass index (p < 0.001) (95.1 +/- 2.1 kg and 35.3 +/- 1.5 kg/m2, respectively) compared with the N-AGPT group (80.1 +/- 0.6 kg and 30.7 +/- 0.6 kg/m2, respectively). Also, the P-AGPT group had significantly lower serum cholesterol (p < 0.02) and triglyceride (p < 0.001) values (4.65 mmol/L and 1.45 mmol/L, respectively) compared with the N-AGPT group (5.51 mmol/L and 2.44 mmol/L, respectively). Two subjects positive for SMAM-1 antibodies had antibodies against each others' serum, suggesting the presence of antigens in one or both. When these two serum samples were inoculated into chicken embryos, macroscopic lesions compatible with SMAM-1 infection developed. The inoculation of serum from N-AGPT subjects did not produce such lesions. The presence of increased obesity, antibodies to SMAM-1, reduced levels of blood lipids, and viremia that produces a typical infection in chicken embryos suggests that SMAM-1, or a serologically similar human virus, may be involved in the cause of obesity in some humans.

Adenoviridae↗