Joseph Vasselli | Columbia University (original) (raw)

Papers by Joseph Vasselli

American Journal of Physiology - Regulatory, Integrative and Comparative Physiology, 2015

Sensory stimulation from foods elicits cephalic phase responses, which facilitate digestion and n... more Sensory stimulation from foods elicits cephalic phase responses, which facilitate digestion and nutrient assimilation. One such response, cephalic-phase insulin release (CPIR), enhances glucose tolerance. Little is known about the chemosensory mechanisms that activate CPIR. We studied the contribution of the sweet taste receptor (T1r2+T1r3) to sugar-induced CPIR in C57BL/6 (B6) and T1r3 knockout (KO) mice. First, we measured insulin release and glucose tolerance following oral (i.e., normal ingestion) or intragastric (IG) administration of 2.8 M glucose. Both groups of mice exhibited a CPIR following oral but not IG administration, and this CPIR improved glucose tolerance. Second, we examined the specificity of CPIR. Both mouse groups exhibited a CPIR following oral administration of 1 M glucose and 1 M sucrose but not 1 M fructose or water alone. Third, we studied behavioral attraction to the same three sugar solutions in short-term acceptability tests. B6 mice licked more avidly for the sugar solutions than for water, whereas T1r3 KO mice licked no more for the sugar solutions than for water. Finally, we examined chorda tympani (CT) nerve responses to each of the sugars. Both mouse groups exhibited CT nerve responses to the sugars, although those of B6 mice were stronger. We propose that mice possess two taste transduction pathways for sugars. One mediates behavioral attraction to sugars and requires an intact T1r2+T1r3. The other mediates CPIR but does not require an intact T1r2+T1r3. If the latter taste transduction pathway exists in humans, it should provide opportunities for the development of new treatments for controlling blood sugar.

Conference proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual Conference, 2005

MRI and image quantitation play an expanding role in modern drug research, because MRI offers hig... more MRI and image quantitation play an expanding role in modern drug research, because MRI offers high resolution and non-invasive ability, and provides excellent soft tissue contrast. Moreover, with development of effective image segmentation and analysis methods, in-vivo and serial tissue growth measurements could be assessed. In the study, MR image acquisition and analysis protocol were established and validated for investigating the effects of anabolic steroids and precursors on muscle growth and body composition in a guinea pig model. Semi-automatic and interactive segmentation methods were developed to accurately label the tissue of interest for tissue volume estimation. In addition, a longitudinal tissue area outlining procedure was proposed for study of tissue geometric features in relation to tissue growth. Finally, a fully automatic data retrieval and analysis scheme was implemented to facilitate the overall huge amount of image quantitation, statistical analysis, as well as s...

Journal of comparative and physiological psychology, 1973

Conducted 6 experiments with 4 female rats in which they were allowed access to Noyes pellets for... more Conducted 6 experiments with 4 female rats in which they were allowed access to Noyes pellets for 1 hr/day with water freely available at all times. The food was presented either ad lib or in a lever-pressing situation on various interval schedules of reinforcement. The size of the individual reinforcements (&amp;quot;bites&amp;quot;) was varied between experiments. Schedule-induced polydipsia was obtained when

Physiology & behavior, 1998

We previously demonstrated that chronic dietary treatment with acarbose, an alpha-glucosidase inh... more We previously demonstrated that chronic dietary treatment with acarbose, an alpha-glucosidase inhibitor, improves glucose homeostasis in the streptozotocin (STZ)-induced diabetic rat. In this study we evaluated the effects of 4 weeks of acarbose treatment on glucose homeostasis in STZ-diabetic rats for both meal-fed (three times daily) and ad libitum feeding conditions. Sprague Dawley male rats (n = 58) were started on a daily meal-feeding paradigm consisting of three 2-h feeding periods: 0700 to 0900 hours, 1300 to 1500 hours, and 1900 to 2100 hours. Following 2 weeks of adaptation, half of the animals were switched to ad libitum feeding. The feeding paradigm itself (meal fed versus ad lib.) affected neither body weight nor daily food intake. Twenty animals from each feeding group then received STZ (60 mg/kg i.v.), whereas control animals received vehicle injections only. Two days later, the diet of 10 STZ-treated animals from each paradigm was supplemented with acarbose (40 mg of ...

Head & neck, Jan 29, 2014

Background: Vandetanib, added to cisplatin and radiation (RT) overcomes chemo RT and EGFR inhibit... more Background: Vandetanib, added to cisplatin and radiation (RT) overcomes chemo RT and EGFR inhibitor resistance in head and neck squamous cell carcinoma (HNSCC) lines and models. Methods: Patients with previously untreated HNSCC received vandetanib daily for 14 days (starting dose 100 mg) then vandetanib +RT (2.2 Gy/day, 5 days/week) for 6 weeks (regimen 1) or vandetanib +RT (2 Gy/day, 5 days/week) + cisplatin (30 mg/m(2) weekly) for 7 weeks (regimen 2). Primary objective was the maximum tolerated dose (MTD) of vandetanib with RT +/- cisplatin. Results: Of 33 treated patients, 30 completed therapy (regimen 1, n=12; regimen 2, n=18). MTD in regimen 2 was 100 mg [3 dose limiting toxicities (DLT) at 200 mg], while regimen 1 was stopped due to poor recruitment (one DLT at 200 mg). Most common grade ≥3 AEs were dysphagia (30%), stomatitis (33%) and mucosal inflammation (27%). Five patients discontinued vandetanib due to AEs. Conclusions: Vandetanib with chemo RT was feasible. Head Neck, 2...

Physiology & Behavior, 1983

MAGG10, C. A., M. R. C. GREENWOOD AND J. R. VASSELLI. The satiety effects of intragastric macronu... more MAGG10, C. A., M. R. C. GREENWOOD AND J. R. VASSELLI. The satiety effects of intragastric macronutrient infusions in fatty and lean Zucker rats. PHYSIOL BEHAV 31(3) 367-372, 1983.--To evaluate satiety in the hyperphagic, genetically obese Zucker "fatty" (fafa) rat, food-deprived fatty and lean (FaFa) control rats were given equicaloric intragastric infusions consisting largely of fat, carbohydrate, or protein. Relative to distilled water infusion, these infusions resulted in immediate reductions of food intake in both fatty and lean rats allowed to feed 20 min post-infusion. Cumulative food intakes remained reduced throughout the 2 hr period of observation. Thus, despite its hyperphagia, the fatty rat is responsive to the satiating effect of infused nutrients. However, the relative satiating effectiveness of the macronutrient infusions differed for the two genotypes. In lean rats, the different macronutrient infusions resulted in equivalent reductions of feeding. In contrast, in fatty rats, fat was the least satiating and protein was the most satiating macronutrient. Moreover, compared to lean rats, fatty rats displayed less initial suppression of feeding after fat infusion and greater overall suppression after protein infusion. These effects are consistent with the long-term feeding behavior of the fatty rat for the different macronutrients and may be related to pre-and postabsorptive metabolic alterations that have been documented in this animal.

Physiology & Behavior, 1980

Development offood motivated behavior in free feeding and food restricted Zucker fatty (fa/fa) ra... more Development offood motivated behavior in free feeding and food restricted Zucker fatty (fa/fa) rats. PHYSIOL. BEHAV. 25(4)565-573, 1980.--The food motivated behavior of ad lib fed or calorically restricted male Zucker fatty and lean rats was compared at 12, 16, 20 and 30 weeks of age. The groups were fasted for 0, 12 and 24 hr and required to lever press for food pellets on V140 sec. Responding by ad lib fatties was elevated over lean controls during the rapid growth period (12 and 16 weeks of age) but was significantly reduced following the completion of growth (20 weeks). Elevated responding accompanied hyperphagia by the ad lib fatties during growth but did not accompany a second, adult onset period of hyperphagia in these fatties. In contrast, fatties calorically restricted from birth responded at elevated rates at all ages compared to lean controls. At 20 weeks restricted fatties, which were as obese on a percentage body composition basis as ad lib fatties, responded significantly more than the latter group at all fasting levels. Metabolic measurements revealed elevated fat cell size, LPL activity/cell and insulin levels in both fatty groups at 15 weeks, and elevated fat cell number in these groups at 33 weeks. The possibility is discussed that enhanced lipogenic factors present during the rapid growth period combine with the metabolic demands of growth to produce a "compensatory hyperphagia" in the fatty rat.

Physiology & Behavior, 1977

WOODS, S. C., J. R. VASSELLI AND K. M. MILAM. Iron appetite and latent learning in rats. PHYSIOL.... more WOODS, S. C., J. R. VASSELLI AND K. M. MILAM. Iron appetite and latent learning in rats. PHYSIOL. BEHAV. 19(5) 623-626, 1977. -Two experiments are reported which show that rats are capable of forming an association between the presence of iron in a solution when it is not specifically needed and a subsequent state of iron deficiency. Specifically, rats were trained to lever press for water while thirsty. One group received ferrous ions in addition to the water. When these rats were subsequently rendered iron deficient, they lever pressed more under extinction conditions as a graded function of lower hemoglobin levels. Controls that either did not receive ferrous ions during training or received solutions other than ferrous solutions during training did not respond this way under extinction conditions. This is therefore a type of latent learning previously demonstrated only for sodium appetite.

Physiology & Behavior, 1988

Although exogenous administration of the peptide cholecystokinin (CCK) has been shown to reduce f... more Although exogenous administration of the peptide cholecystokinin (CCK) has been shown to reduce food intake in a variety of experimental situations, few studies have examined the influence of dietary content upon CCK's effectiveness, particularly in obese states. To evaluate the effectiveness of CCK administration in animals consuming high fat diets, groups of obese and lean Zucker rats were maintained on laboratory chow (CH), a high fat diet isocaloric to chow (IF), or a hypercaloric fat diet (HF). After a 17 hr fast, rats were given intraperitoneal injections of saline or ascending doses of 0.06 to 2.0 micrograms/kg of the synthetic octapeptide of CCK. On all diets, obese rats required higher doses of CCK to significantly reduce feeding and showed smaller intake reductions than lean rats (p less than 0.001). Despite higher baseline caloric intakes (p less than 0.001), rats of both genotypes maintained on HF displayed larger reductions of intake than those fed IF or CH (p less than 0.001). Intake reductions by either genotype maintained on IF or CH were not reliably different. The manner in which the satiety effect of CCK was enhanced in rats consuming the calorically dense, palatable HF diet is unclear but may be related to orosensory and/or postingestive attributes of the diet.

Pharmacology Biochemistry and Behavior, 1983

Effects ofa glucosidase inhibitor (acarbose, BAY g 5421) on the development of obesity and food m... more Effects ofa glucosidase inhibitor (acarbose, BAY g 5421) on the development of obesity and food motivated behavior in Zucker (fafa) rats. PHARMACOL BIOCHEM BEHAV 19(1) [85][86][87][88][89][90][91][92][93][94][95] 1983.--BAY g 5421 (acarbose) inhibits carbohydrate digestion in the gut, thereby reducing the rate or glucose absorpUon. This experiment tested whether long term administration of acarbose" to developing Zucker "fatty" (fafa) rats would, by reducing several lipogenic factors, attenuate lipid deposition and reduce the hyperphagia and increased food motivated behavior of these animals. From 7 to 20 weeks of life groups of fatty and lean (FaFa) control rats were fed 0, 20 or 40 nag acarbose/100 g maintenance diet (45% carbohydrate, 35% fat, 20% protein calories), while an additional fatty and lean group were pair-fed to respective 40 mg acarbose groups. Lean groups fed acarbose exhibited dose dependent reductions of body weight, insulin, triglycerides, retroperitoneal and epididymal pad weight, adipocyte size, LPL activity/cell (retroperitoneal pad only), and lipid deposition both in total grams of fat and as a percentage of carcass weight. Fatty groups fed acarbose exhibited dose dependent reductions of insulin, blood glucose, retroperitoneal pad weight, and, at one of the two doses used, significantly lowered body weight, (40 mg), triglycerides (20 rag) and cholesterol (20 rag). However, acarbose-fed fatty groups failed to show significant reductions of adipocyte size, number or LPL activity/cell in retroperitoneai and epididymal fat pads, and maintained their obese body composition, on a percentage basis, at levels not significantly different from that of the 0 mg fatty control group. Acarbose administration led to an intitial dose dependent reduction of food intake in both genotypes, which persisted for the lean groups. Fatties fed the 20 mg dose showed a gradual tendency (ns) towards increased daily intake, lever pressed at elevated rates for food pellets, and refed at faster rates following fasting. Fatties fed the 40 mg dose maintained their daily intake at fatty control levels, did not lever press at elevated rates, and showed significantly reduced refeeding following fasting. The 40 mg fatty and both lean acarbose treated groups had decreased sucrose solution preference. Possible bases for these differing effects of the drug on feeding behavior by the groups are considered.

Obesity, 2007

The anti-diabetic thiazolidinediones (TZDs) stimulate adipocyte differentiation and decrease mean... more The anti-diabetic thiazolidinediones (TZDs) stimulate adipocyte differentiation and decrease mean adipocyte size. However, whether these smaller, more insulin-sensitive adipocytes maintain their size after TZD therapy is discontinued has not been studied. Adult female Sprague-Dawley rats were fed a low-fat (10% fat) diet or, to elevate body weight (BW), a high-fat (HF) diet (45% fat) for 6 weeks. Rats were initially randomized to groups (n = 12) fed either low-fat or HF diets, with or without the TZD rosiglitazone (ROSI; 5 mg/kg per day), for 6 weeks. ROSI was then discontinued, and all animals were fed HF for another 6 weeks before sacrifice. Retroperitoneal (RP) adipose tissue morphology was determined from tissue collected by serial biopsies before and after 6 weeks of ROSI treatment and at sacrifice. Measures of BW and adiposity did not differ among groups 6 weeks after stopping ROSI treatment. However, during treatment, ROSI in both diets significantly decreased RP adipocyte size and increased RP DNA content, and these effects continued to be observed after discontinuing treatment. ROSI administration also decreased circulating insulin, leptin, and triglycerides and increased circulating adiponectin levels; however, these effects were reversed on stopping treatment. These results demonstrated that TZD-induced effects on adipocyte size and number were maintained after discontinuing treatment, even with consumption of an obesigenic diet. However, additional studies are needed to determine whether TZD-treated animals eventually achieve an adipocyte size similar to that of untreated animals at the expense of a higher BW.

Obesity, 2005

Intentional weight loss reduces mortality rate in a rodent model of dietary obesity. Obes Res. 20... more Intentional weight loss reduces mortality rate in a rodent model of dietary obesity. Obes Res. 2005;13:693-702. Objective : We used a rodent model of dietary obesity to evaluate effects of caloric restriction-induced weight loss on mortality rate.

Metabolism, 1991

Diabetes is characterized by hyperphagia, polydipsia, polyuria, and elevations in blood and urina... more Diabetes is characterized by hyperphagia, polydipsia, polyuria, and elevations in blood and urinary glucose. It has also been documented that (3-adrenergic responsiveness is reduced in diabetes. The intestinal glucosidase inhibitor, acarbose (BAY G 5421), decreases postprandial glycemia by delaying carbohydrate absorption. The purpose of this study was to evaluate the effects of chronic acarbose treatment (20 and 40 mg/lOO g of diet) on the metabolic and adrenergic parameters altered in streptozotocin (STZ) (50 mg/ kg, intravenously [IV])-induced diabetes. Metabolic parameters were measured daily for 8 weeks.

Complementary Therapies in Medicine, 1999

Context.-Hydroxycitric acid, the active ingredient in the herbal compound Garcinia cambogia, comp... more Context.-Hydroxycitric acid, the active ingredient in the herbal compound Garcinia cambogia, competitively inhibits the extramitochondrial enzyme adenosine triphosphate-citrate (pro-3S)-lyase. As a citrate cleavage enzyme that may play an essential role in de novo lipogenesis inhibition, G cambogia is claimed to lower body weight and reduce fat mass in humans.

Annals of the New York Academy of Sciences, 2006

Magnetic resonance imaging (MRI) has potential as an instrument to measure body composition becau... more Magnetic resonance imaging (MRI) has potential as an instrument to measure body composition because it can discriminate various soft tissues in vivo. These soft tissues include adipose tissue, muscle, organs, and brain. We report on preliminary studies using a 4.2-tesla MRI for measuring body composition in the mouse and rat. We employed image segmentation methods that include an image correction method, a necessary requirement when the images are taken in the presence of nonuniform radio-frequency (RF) coil response. The software for 3-D data segmentation, quantification, correction, image manipulation, and visualization has been developed as a research tool. This method currently is being validated.