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61.
62.
Dhurandhar NV 《The Lancet infectious diseases》2011,11(12):963-969
WHO has declared obesity to be a global epidemic. Obesity management strategies mainly target behavioural components of the disorder, but are only marginally effective. A comprehensive understanding of the causative factors of obesity might provide more effective management approaches. Several microbes are causatively and correlatively linked with obesity in animals and human beings. If infections contribute to human obesity, then entirely different prevention and treatment strategies and public health policies could be needed to address this subtype of the disorder. Ethical reasons preclude experimental infection of human beings with candidate microbes to unequivocally determine their contribution to obesity. As an alternative, the available information about the adipogenic human adenovirus Ad36 has been used to create a template that can be used to examine comprehensively the contributions of specific candidate microbes to human obesity. Clinicians should be aware of infectobesity (obesity of infectious origin), and its potential importance in effective obesity management. 相似文献
63.
Suhadinie Gamage P. Hemachandra Reddy Nikhil V. Dhurandhar Vijay Hegde 《Journal of diabetes and its complications》2019,33(3):261-265
Aging constitutes a major risk factor for the development of type-2 diabetes (T2D) where glucose tolerance declines with age, resulting in a high prevalence of T2D and impaired glucose tolerance in the elderly population. Currently more than half of the 20 million U.S. adults with T2D are above the age of 60, and the largest increase in T2D prevalence is expected in the elderly. Obesity is a causative factor for T2D associated insulin resistance and hyperglycemia. Furthermore, the aging process is accelerated by hyperglycemia and effective treatment options are limited for the vulnerable aging population. One of the mechanisms contributing to aging associated hyperglycemia is resistance to insulin-mediated glucose disposal. Chronic hyperglycemia also accelerates aging by increasing pro-inflammatory milieu leading to impaired immune function. Although currently available anti-diabetic agents improve glycemic control, they have potential serious side effects in some cases. Therefore, additional and better drugs are urgently needed for treatment of insulin resistance and aging associated health risk factors. This review presents the novel use of a microbial protein, E4orf1 as a potential anti-diabetic agent, which functions independent of insulin and obesity, highlighting the role of unique sources for future drug development. 相似文献
64.
Infectious etiology is implicated in chronic diseases such as gastric ulcer or atherosclerosis. However, “infection” is a recent term in the field of obesity. Since the first report in 1982 of obesity due to infection, several microbes have been linked to obesity. Among the adipogenic microbes, avian adenovirus SMAM‐1 and human adenovirus Ad36 have been studied most extensively for the past 25 years. Here, we present a systematic review of literature about SMAM‐1 and Ad36. Reports from North America, Europe, and Asia reveal strong evidence that Ad36 causes obesity in animals and paradoxically improves glycemic control, and in vitro data provides mechanistic explanation. Considering that experimental Ad36 infection of humans is unlikely, its causative role in human obesity or glycemic control has not been demonstrated unequivocally. Nonetheless, most, but not all, observational studies in children and adults link Ad36 infection to obesity and improvement in glycemic control. The E4orf1 gene of Ad36 was identified as responsible for better glycemic control. Overall, 25 years have considerably advanced knowledge about the role of infection in obesity. Potential translational benefits include the development of vaccines to prevent Ad36‐induced obesity and drug development based on the E4orf1 protein to improve glycemic control. 相似文献
65.
Dubuisson O Dhurandhar EJ Krishnapuram R Kirk-Ballard H Gupta AK Hegde V Floyd E Gimble JM Dhurandhar NV 《Endocrinology》2011,152(10):3648-3660
Although thiazolidinediones (TZD) effectively improve hyperglycemia and increase adiponectin, a proinsulin-sensitizing adipokine, they also increase adipogenesis via peroxisome proliferator-activated receptor (PPAR)γ induction, which may be undesirable. Recent safety concerns about some TZD have prompted the search for next generation agents that can enhance glycemic control and adiponectin independent of PPARγ or adipogenesis. Reminiscent of TZD action, a human adenovirus, adenovirus 36 (Ad36), up-regulates PPARγ, induces adipogenesis, and improves systemic glycemic control in vivo. We determined whether this effect of Ad36 requires PPARγ and/or adipogenesis. Glucose uptake and relevant cell signaling were determined in mock-infected or human adenoviruses Ad36 or Ad2-infected cell types under the following conditions: 1) undifferentiated human-adipose-tissue-derived stem cells (hASC), 2) hASC differentiated as adipocytes, 3) hASC in presence or absence of a PPARγ inhibitor, 4) NIH/3T3 that have impaired PPARγ expression, and 5) PPARγ-knockout mouse embryonic fibroblasts. Mouse embryonic fibroblasts with intact PPARγ served as a positive control. Additionally, to determine natural Ad36 infection, human sera were screened for Ad36 antibodies. In undifferentiated or differentiated hASC, or despite the inhibition, down-regulation, or the absence of PPARγ, Ad36 significantly enhanced glucose uptake and PPARγ, adiponectin, glucose transporter 4, and glucose transporter 1 protein abundance, compared with mock or Ad2-infected cells. This indicated that Ad36 up-regulates glucose uptake and adiponectin secretion independent of adipogenesis or without recruiting PPARγ. In humans, natural Ad36 infection predicted greater adiponectin levels, suggesting a human relevance of these effects. In conclusion, Ad36 provides a novel template to metabolically remodel human adipose tissue to enhance glycemic control without the concomitant increase in adiposity or PPARγ induction associated with TZD actions. 相似文献
66.
Wang S Ferguson KC Burris TP Dhurandhar NV 《Expert opinion on investigational drugs》1999,8(7):1117-1125
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. 相似文献
67.
Vander Wal JS Marth JM Khosla P Jen KL Dhurandhar NV 《Journal of the American College of Nutrition》2005,24(6):510-515
OBJECTIVE: To test the hypotheses that among overweight and obese participants, a breakfast consisting of eggs, in comparison to an isocaloric equal-weight bagel-based breakfast, would induce greater satiety, reduce perceived cravings, and reduce subsequent short-term energy intake. SUBJECTS: Thirty women with BMI's of at least 25 kg/M2 between the ages of 25 to 60 y were recruited to participate in a randomized crossover design study in an outpatient clinic setting. DESIGN: Following an overnight fast, subjects consumed either an egg or bagel-based breakfast followed by lunch 3.5 h later, in random order two weeks apart. Food intake was weighed at breakfast and lunch and recorded via dietary recall up to 36 h post breakfast. Satiety was assessed using the Fullness Questionnaire and the State-Trait Food Cravings Questionnaire, state version. RESULTS: During the pre-lunch period, participants had greater feelings of satiety after the egg breakfast, and consumed significantly less energy (kJ; 2405.6 +/- 550.0 vs 3091.3 +/- 445.5, Egg vs Bagel breakfasts, p < 0.0001), grams of protein (16.8 +/- 4.2 vs 22.3 +/- 3.4, Egg vs Bagel breakfasts, p < 0.0001), carbohydrate 83.1 +/- 20.2 vs 110.9 +/- 18.7, Egg vs Bagel breakfasts, p < 0.0001), and fat 19.4 +/- 5.1 vs 22.8 +/- 3.2, Egg vs Bagel breakfasts, p < 0.0001) for lunch. Energy intake following the egg breakfast remained lower for the entire day (p < 0.05) as well as for the next 36 hours (p < 0.001). CONCLUSIONS: Compared to an isocaloric, equal weight bagel-based breakfast, the egg-breakfast induced greater satiety and significantly reduced short-term food intake. The potential role of a routine egg breakfast in producing a sustained caloric deficit and consequent weight loss, should be determined. 相似文献
68.
Vander Wal JS Waller SM Klurfeld DM McBurney MI Cho S Kapila M Dhurandhar NV 《International journal of food sciences and nutrition》2006,57(1-2):97-106
The objectives of this study were to examine whether providing a structured post-dinner snack would enhance weight loss among obese night snackers participating in a novel partial meal replacement (PMR) program and to examine the efficacy of that program. Sixty adults (age 18-65 years; body mass index >or=30 kg/m2), 29 randomized to the 'post-dinner snack' and 32 to the 'no snack' groups, completed the 8-week program. Both groups showed improvements in weight (-4.23 kg, P < 0.0001), body mass index (-1.48 kg/m2, P < 0.0001), body fat (-1.36%, P < 00.0001), waist circumference (-6.40 cm, P < 0.0001), and high-density lipoprotein-cholesterol (-2.72 mmol/l, P < 0.01), and on a night snacking question (-1.31, P < 0.0001). The 'post-dinner snack' group did not show significantly greater weight loss outcomes than the 'no snack' group either before or after taking compliance into consideration. Providing a structured post-dinner snack along with a PMR program did not enhance weight loss treatment outcomes; however, the PMR program produced beneficial weight loss changes for obese night snackers. 相似文献
69.
H N Dhurandhar C Brown J Barrett M S Litwin 《Archives of pathology & laboratory medicine》1979,103(7):335-340
Blood stored under standard blood band conditions develops microaggregates of platelets and leukocytes. Dog lungs were studied by light and electron microscopy at intervals from 48 hours to six days following exchange transfusions of sublethal volumes of such microaggregate-rich blood through either standard or Dacron wool (Swank) transfusion filters. After transfusion through standard filters, the pulmonary microvasculature was extensively occluded by microemboli. Swelling of capillary endothelial cells, interstitial and alveolar edema, and hypoxic changes in types I and II alveolar epithelial cells were noted. Changes then progressively resolved. These detrimental changes were prevented when microaggregates were removed by Dacron wool (Swank) filters. Mechanical occlusion of the pulmonary vasculature probably plays a minor role in initiating the structural changes observed. Release of lysosomes from disintegrating microaggregates is believed to be the significant factor initiating a chain of events leading to progressive pulmonary damage. 相似文献
70.
The world is currently experiencing an obesity epidemic as declared by the World Health Organization. The traditional view is that behaviour leading to overeating and under-activity is the major contributing factor for this worldwide epidemic. However, several microbes are linked to obesity in animals and humans. On the one hand, various microbes, including animal and human viruses, bacteria, parasites and scrapie agents, increase adiposity in several animal models. Some of these microbes show an association with human obesity, but conclusive evidence for a causative role of microbes in human obesity is lacking. On the other hand, obese individuals show an altered response to infections. Obesity is often associated with impaired immune function, which may lead to increased susceptibility to infection with a number of different pathogens. Hence, certain microbes appear to induce obesity, whereas, obesity itself may exacerbate certain other infections. Linking the two phenomenon is the immunological property of adipocytes and their progenitors. For instance, proliferating pre-adipocytes share embryonic origin with immune cells and exhibit phagocytic activity. Taken together it appears that there is a close interrelationship between adipose tissue, inflammatory response, immune system and infections. Hence, it is conceivable that in response to certain infections, adipose tissue expands similar to the expansion of cells of the immune system. The impaired immune function of adipose tissue in obesity may exacerbate infections. Considering the global obesity epidemic, it is necessary to further investigate both phenomena. 相似文献