Papers by MaryAnne DellaFera
Obesity, 2014
Dr. Clifton A. Baile, whose research career spanned half a century combining activities in both a... more Dr. Clifton A. Baile, whose research career spanned half a century combining activities in both academia and industry, died on May 19, 2014. Cliff's research on the regulation of energy balance and growth and on muscle and adipose tissue physiology is internationally acclaimed, and throughout his career, he sought to translate new basic knowledge about physiological mechanisms into economically viable applications.
Neuroscience letters, 1987
Kcywordsv Cholecystokinin; Dynorphin, Met-enkephalin; Hypothalamus; Immunohistochemistry:
Biochemical and biophysical research communications, 2008
Apelin, the endogenous ligand of the G protein-coupled APJ receptor has been shown to promote tum... more Apelin, the endogenous ligand of the G protein-coupled APJ receptor has been shown to promote tumor angiogenesis. However, the effect of apelin on inducing angiogenesis in adipose tissue has not been investigated. In this review, we propose a putative role for apelin in promoting angiogenesis in adipose tissue. We further propose that targeting adipose tissue vasculature by blocking apelin signaling with anti-apelin antibodies will lead not only to inhibition of angiogenesis in adipose tissue but also to decreased adiposity.
Physiology & behavior, 1990
Cholecystokinin (CCK) and neuropeptide Y (NPY) have been implicated in the control of food intake... more Cholecystokinin (CCK) and neuropeptide Y (NPY) have been implicated in the control of food intake in a number of species. This study was carried out to determine 1) whether nutrient-related stimulation of the upper small intestine could activate central CCK and NPY neuronal systems, resulting in changes in concentration of these peptides in specific brain areas, and 2) the influence of the circadian cycle on nutrient-related effects. Four groups of rats received treatments of either 1.0 ml saline (S) or Ensure liquid diet (E) infused into the duodenum either during the dark (D) or light (L) phase of the circadian cycle. CCK and NPY concentrations in extracts of specific brain areas were measured by RIAs. CCK concentration in the supraoptic n. (SON) was higher in D than in L, regardless of infusion treatment, and in the dorsal parabrachial n. area (DPN), CCK concentration was higher in E than S infused rats, regardless of circadian phase. CCK concentration in the dorsal motor vagal n. area (DMV) was higher in E, but only during L. NPY concentration was higher in DPN and paraventricular n. areas (PVN) and lower in the suprachiasmatic n. area (SC) after E, regardless of circadian phase. The changes in concentration of CCK and NPY in specific brain areas in response to food in the upper intestine suggest that nutrient-related signals from the intestine can activate specific CNS CCK and NPY-containing neural pathways.
Domestic animal endocrinology, 2004
-Adrenergic receptor (-AR) agonists increase muscle mass and decrease body fat in rodents and l... more -Adrenergic receptor (-AR) agonists increase muscle mass and decrease body fat in rodents and livestock. With oral administration, however, the effects of 1-AR and 2-AR can be different, depending on the species tested. We tested the effects of clenbuterol, a 2-AR agonist, and ractopamine, a 1/2-AR agonist, on growth, adiposity and adipose tissue apoptosis in male and female mice by feeding diets containing control, 200 ppm clenbuterol, or 200 or 800 ppm ractopamine. Food intake (FI) was measured daily; body weight (BW) and temperatures (BT) were measured on days 0, 3, 7, 10, 14, 17, and 20. On day 21 mice were sacrificed, body composition was determined using PIXImus densitometry, and muscle and adipose tissues were collected. There were no treatment effects on BT, FI, BW, feed efficiency or body composition. Retroperitoneal (Rp) and epididymal/parametrial (Epi/Par) fat pad masses were reduced in both 800 ppm ractopamine (40±3 mg and 207±20 mg, respectively) and clenbuterol (35±7 mg and 211±22 mg) treated mice compared to control (66 ± 8 mg and 319 ± 30 mg, P < 0.05). Brown adipose tissue (BAT) mass was greater (P < 0.05) in clenbuterol treated mice compared to other treatments. Adipose tissue apoptosis (% DNA fragmentation) was increased in Epi/Par fat pads in clenbuterol (5.2 ± 1.1%) and 800 ppm ractopamine (4.1 ± 0.8%) treated mice compared to control (1.7 ± 0.4%, P < 0.05). These findings show that WAT apoptosis can be induced by activation of -AR in mice, although the mechanism is unknown.
Journal of medicinal food, 2009
The effect of octanoate and decanoate, respectively, eight- and 10-carbon medium-chain fatty acid... more The effect of octanoate and decanoate, respectively, eight- and 10-carbon medium-chain fatty acids (MCFAs), on apoptotic signaling in 3T3-L1 adipocytes was investigated. 3T3-L1 adipocytes were treated with various concentrations of octanoate or decanoate. Cell viability, apoptosis, and expression of apoptosis-related proteins were investigated. Results indicated that both octanoate and decanoate decreased viability, increased apoptosis, and increased reactive oxygen species production. Immunoblotting analysis showed an increase in the levels of cytoplasmic cytochrome c and cleaved poly(ADP-ribose) polymerase by octanoate and decanoate. Concomitantly, we observed that pro-caspase-3 was decreased, resulting in the induced accumulation of the cleaved form of caspase-3 by both octanoate and decanoate. In addition, both octanoate and decanoate increased the expression of pro-apoptotic Bax with an accompanied decrease of anti-apoptotic Bcl-2. These results show that octanoate and decanoate mediate adipocyte apoptosis via a caspase-dependent mitochondrial pathway in 3T3-L1 adipocytes. MCFAs thus decrease adipocyte number by initiating the apoptotic process in 3T3-L1 adipocytes.
Obesity (Silver Spring, Md.), 2008
Objective: To determine the effects of guggulsterone (GS), the active substance in guggulipid, on... more Objective: To determine the effects of guggulsterone (GS), the active substance in guggulipid, on apoptosis, adipogenesis, and lipolysis using 3T3-L1 cells.Methods and Procedures: For apoptosis and lipolysis experiments, mature adipocytes were treated with GS isomers. Viability, apoptosis, and caspase 3/7 activation were quantified using MTS, enzyme-linked immunosorbent assay (ELISA), caspase-Glo 3/7 activity assay, respectively. The expression of cytochrome c was demonstrated by western blot. Lipolysis was quantified by measuring the release of glycerol. For adipogenesis experiments, postconfluent preadipocytes were incubated with GS isomers for up to 6 days during maturation. Adipogenesis was quantified by measuring lipid content using Nile Red dye. Western blot was also used to demonstrate the adipocyte-specific transcription factors peroxisome proliferator–activated receptor γ2 (PPARγ2), CCAAT/enhancer binding protein α (C/EBPα), and C/EBPβ.Results: In mature adipocytes cis-GS decreased viability, whereas the trans-GS isomer had little effect. Both isomers caused dose-dependent increases in apoptosis and cis-GS was more effective than trans-GS in inducing apoptosis. cis- and trans-GS also increased caspase-3 activity and release of cytochrome c from mitochondria. In maturing preadipocytes, both isomers were equally effective in reducing lipid content. The adipocyte-specific transcription factors PPARγ2, C/EBPα, and C/EBPβ were downregulated after treatment with cis-GS during the maturation period. Furthermore, cis-GS increased basal lipolysis of mature adipocytes, but trans-GS had no effect.Discussion: These results indicate that GS isomers may exert antiobesity effects by inhibiting differentiation of preadipocytes, and by inducing apoptosis and promoting lipolysis of mature adipocytes. The cis-GS isomer was more potent than the trans-GS isomer in inducing apoptosis and lipolysis in mature adipocytes.
Physiology & behavior, 1981
with CCK-like activity administered intracranially elicit satiety in sheep. PHYSIOL. BEHAV. 26(6)... more with CCK-like activity administered intracranially elicit satiety in sheep. PHYSIOL. BEHAV. 26(6) [979][980][981][982][983] 1981--Cholecystokinin (CCK) peptides and receptors have been shown to be present in the brain as well as in gastrointestinal organs. While functions for peripheral CCK are well recognized, those for central CCK peptides are only now being investigated. We have shown previously that CCK-octapeptide (CCK-OP) is a very potent and specific suppressor of feeding when administered in the cerebral ventricles of sheep. In the present study the objective was to determine the relative potency of several CCK analogues in inhibiting feeding when administered as 75 min continuous injections into the lateral cerebral ventricles of 2-hr fasted sheep. In comparing feeding response during CCK-OP injections to that during caerulein injections, it was found that feed intakes were similar only at an equal molar dose (0.638 pmole/min); whereas three times as much CCK-33 (1.91 pmoles/min) as CCK-OP (0.638 pmoles/min) was required to produce similar feed intakes. Both caerulein (0.638 pmoles/min) and CCK-33 (1.91 pmoles/min) caused significant decreases in feeding compared to control (sCSF). Desuifated CCK-OP had no effect on feeding at a dose (0.638 pmoles/min) that causes 80-100% decreases in feeding when the C-7 tyrosine is sulfated. Feed intake was significantly less with 2.55 pmolesdmin CCK-OP than with an equal dose of desulfated CCK-OP. These results concur with those of previous studies on specific CCK receptors in the pancreas and in the brain, and therefore support the concept of specific CCK receptors in brain having a role in satiety.
Apoptosis : an international journal on programmed cell death, 2003
Great strides have been made in understanding the genetics of body weight regulation, in part due... more Great strides have been made in understanding the genetics of body weight regulation, in part due to the study of rodent models of obesity that are characterized by mutations affecting leptin or its receptors. Leptin, produced in adipose tissue, acts both centrally and peripherally to orchestrate complex metabolic and behavioral changes that increase loss of adipose tissue, including suppressing food intake and increasing thermogenesis. In addition, recent evidence indicates that leptin acts centrally to trigger an apoptotic process resulting in adipocyte deletion. Loss of adipocytes by apoptosis may provide an explanation for the unexpected delay in return to initial energy status following leptin treatments. This review summarizes the major aspects of leptin-induced adipose tissue apoptosis, including some of the newest findings about possible mechanisms of action.
The Journal of nutrition, 2007
Genistein (G) and resveratrol (R) individually inhibit adipogenesis in 3T3-L1 adipocytes and indu... more Genistein (G) and resveratrol (R) individually inhibit adipogenesis in 3T3-L1 adipocytes and induce apoptosis in cancer cells.
Journal of physiology and biochemistry, 2010
Clenbuterol, a beta2-adrenergic receptor (β2-AR) selective agonist, has been shown to decrease bo... more Clenbuterol, a beta2-adrenergic receptor (β2-AR) selective agonist, has been shown to decrease body fat in animals and can induce apoptosis in adipose tissue in mice. We hypothesized that direct actions of a β-adrenergic receptor agonist on adipocytes could trigger the observed apoptotic effect. The hypothesis was inspected by investigating the direct effect of clenbuterol on apoptosis, adipogenesis, and lipolysis in vitro using the 3T3-L1 cell line and rat primary adipocytes. Cells were treated with 10−9 to 10−5 M clenbuterol depending on the experiments. There was no apoptotic effect of clenbuterol both in 3T3-L1 cells and rat primary adipocytes. Adipogenesis monitored by Oil Red O staining and AdipoRed™ assay was modestly decreased by clenbuterol treatment (p < 0.05). In fully differentiated primary adipocytes, clenbuterol increased basal lipolysis compared with the control (p < 0.01). In summary, direct stimulation of β2-AR by clenbuterol does not cause apoptosis in adipocytes, despite a direct lipolytic stimulation and attenuation of adipogenesis.
Endocrine, 2010
This study compared the central effects of ghrelin and leptin on body and bone marrow adiposity a... more This study compared the central effects of ghrelin and leptin on body and bone marrow adiposity and gene expression in adipose tissue and bone marrow. Male Sprague–Dawley rats were injected intracerebroventricular (ICV) twice daily with control, 66 ng ghrelin (G66), 330 ng ghrelin (G330), or 5 μg leptin (L5) for 5 days. Food intake (FI) and body weight (BW) were measured daily. Gene expression in adipose tissue and bone marrow was assessed using RT–PCR. Leptin reduced FI (P < 0.05) and BW (P < 0.05), whereas ghrelin increased BW (P < 0.05) without affecting FI. Leptin decreased fat pad weights, whereas ghrelin (G330) increased fat pad weights (P < 0.05). In epididymal adipose tissue, leptin increased expression of lipolysis marker ADRB2 and thermogenesis marker MFN2 and decreased expression of adipogenic markers, FASN, SLC2A4, and SCD1, whereas ghrelin increased expression of FASN and SCD1. Leptin decreased bone marrow adipocyte size and number; however, ghrelin had no effect on these parameters. In whole bone marrow, leptin decreased expression of FASN and SCD1 and increased expression of DLK1, whereas ghrelin (G330) decreased expression of COL1A1. Thus, leptin induces similar changes in bone marrow and adipose tissue gene expression, reflecting the decreased adiposity in both compartments.
Physiology & behavior, 1990
We tested the hypothesis that blockade of central alpha 2-adrenergic receptors would prevent neur... more We tested the hypothesis that blockade of central alpha 2-adrenergic receptors would prevent neuropeptide Y (NPY)-induced feeding. Nine young female sheep were fitted with lateral ventricula cannulas. Bolus intracerebroventricular (ICV) injection of 3 nmol of NPY increased feed intake after 30 min between 45 and 153% in three experiments. A bolus ICV injection of 400 or 100 nmol of the alpha 2-antagonist, yohimbine, either 5 or 30 min before NPY injection, did not attenuate this response. Instead, yohimbine increased feed intake over NPY-induced feeding by 52 to 55%. We interpret these data as evidence that the putative NPY feeding pathway in feed-sated sheep is not dependent on the type of alpha 2-adrenergic mechanism which can be blocked by ICV injection of yohimbine.
Peptides
ventricular transport and uptake: Importance of [963][964][965][966][967][968] 1982.--Brain chole... more ventricular transport and uptake: Importance of [963][964][965][966][967][968] 1982.--Brain cholecystokinin (CCK) pep(ides have been proposed to be involved in the control of feed intake. We have examined the importance of the cerebral ventricular system in CCKmediated satiety in sheep. Continuous injection of 0.64 pmol/min CCK-8 into the lateral ventricles (LV) decreased feeding, whereas injection of neither 0.64 nor 2.55 pmol/min CCK-8 into the cisterna magna (CM) significantly affected feeding. Thus, it is likely that the rostral, but not caudal, ventricular compartments and/or adjacent brain areas are involved in CCK-8 mediated satiety. The rate of injection of carrier solution (synthetic cerebrospinal fluid [sCSF]) was found to affect feed intake during a continuous 75 min injection: feed intakes were greater during injection of sCSF at 0.10 ml/min than during either 0.03 ml/min sCSF or no injection (sham). Injection of 0.64 pmol/min CCK-8 in either 0.03 or 0.10 ml/min decreased feeding. The increased feeding during 0.10 ml/min sCSF injection may have been due to dilution of endogenous CCK released into CSF during the meal. To determine the percent recovery from CSF of exogenous CCK-8, CSF samples from CM were collected during 3 hr continuous LV injections of CCK-8 and inulin (for measurement of bulk absorption). Only 20 to 40 percent of administered CCK-8 was recovered in CM CSF. The loss of CCK-8 was probably not due to degradation in the CSF by proteolytic enzymes, since CCK-8 concentrations did not decrease during in vitro incubation at 37°C for up to 24 hr. We propose that CCK-8 is released during feeding into the ventricular system, and subsequently taken up from CSF by specialized ependymal cells for transport to sites of action.
Archives of oral biology, 1995
Sununary---Chlorhexidine gluconate at a dose used to control bacteria in the mouth has a reversib... more Sununary---Chlorhexidine gluconate at a dose used to control bacteria in the mouth has a reversible effect on taste perception. Taste-intensity ratings and taste-quality identification for concentration series of sucrose, sodium chloride, citric acid and quinine hydrochloride were obtained from 15 healthy humans. The participants rinsed with 0.12% chlorhexidine for 3 rain twice a day. Each individual was tested 3 times: before the 4-day rinse period, 30 min after the final rinse, and 4 days after the rinse period. Chlorhexidine rinses reduced the perceptual intensity of sodium chloride and quinine hydrochloride, not sucrose or citric acid. No effects on taste perception were detected 4 days after the rinse period. The identification of sodium chloride as sally was seriously impaired by chlorhexidine but the identification of quinine hydrochloride as bitter was not affected. Specific sites of action of chlorhexidine on the taste epithelium are not known but its effects on salty taste may be related to its strong positive charge and its effect on bitter taste may be related to its amphiphilicity. Chlorhexidine has promise as a probe of taste transduction, as well as for the management of salty/bitter dysgeusias in humans.
The American journal of physiology, 1989
We compared the effects of neuropeptide Y (NPY) injected into the lateral ventricle (LV) and peri... more We compared the effects of neuropeptide Y (NPY) injected into the lateral ventricle (LV) and periphery (ip in rats; iv in sheep) on feed and water intake. In sated rats, a bolus injection of 1.18 or 2.35 nmol of NPY administered LV, but not ip, increased (P less than 0.05) feed intake on average of 809% within 30 min of injection. In sated sheep, an LV bolus injection of 2.35 nmol of NPY increased feed intake by 154% within 30 min. Similar doses of human pancreatic polypeptide and peptide YY were less orexigenic than NPY in sheep. After 24 h, cumulative feed intakes were similar among control and peptide treatments. Intravenous injection of 2.35 nmol NPY did not increase feed intake in sheep. Water intake was stimulated (P less than 0.05) by NPY (LV injection) in both the presence and absence of feed. We propose that NPY is involved in the central regulation of consummatory behavior in sheep.
Annals of the New York Academy of Sciences, 1985
Obesity (Silver Spring, Md.), 2008
Objective: To investigate the ability of 1,25(OH)2D3 (D) and genistein (G), alone and in combinat... more Objective: To investigate the ability of 1,25(OH)2D3 (D) and genistein (G), alone and in combination, to inhibit adipogenesis and induce apoptosis in 3T3-L1 adipocytes.Methods and Procedures: 3T3-L1 preadipocytes and mature adipocytes were incubated with various concentrations of D and G, alone and in combination, for 48 h. Viability was determined using the Cell Titer 96 Aqueous One Solution Cell Proliferation Assay. Post-confluent preadipocytes were incubated with D and G for up to 6 days during adipogenesis and lipid content was quantified by Nile Red dye; apoptosis was quantified by measurement of single-stranded DNA. Expression of adipocyte-specific proteins and VDR was analyzed by western blotting.Results: Combining D and G did not cause an enhanced effect on cell viability in either preadipocytes or mature adipocytes. In maturing preadipocytes, D at 0.5 nmol/l (D0.5) increased apoptosis by 47 ± 10.25% (P < 0.05) and inhibited lipid accumulation by 28 ± 10% (P < 0.001), while G at 25 μmol/l (G25) had no significant effect. However, D+G caused an enhanced apoptosis by 136 ± 12.6% (P < 0.001) and enhanced inhibition of lipid accumulation by 82.46 ± 2.95% (P < 0.001). Similarly, D0.5 alone decreased adipose-specific gene 422 (aP2) expression to 34.2 ± 2.3% and increased VDR expression levels by 41.8 ± 11% (P < 0.001), but G25 showed no effect. However, D0.5+G25 decreased aP2 expression to 52 ± 4.2% (P < 0.05) and increased VDR expression levels by 131 ± 14.5% (P < 0.0001).Discussion: These findings suggest that combining 1,25(OH)2D3 with genistein results in an enhanced inhibition of lipid accumulation and induction of apoptosis in maturing 3T3-L1 preadipocytes.
Federation proceedings, 1984
Roles of brain and intestinal peptides in the control of food intake may vary among species for s... more Roles of brain and intestinal peptides in the control of food intake may vary among species for specific peptides depending on the degree of complexity of the gastrointestinal tract. Cholecystokinin (CCK) in the brain and intestine is the most widely studied of the peptides involved in the control of feeding. Although CCK released from the intestine may act on peripheral receptors in producing satiety in the pig, a monogastric animal, it has little effect on feeding after peripheral administration in sheep. CCK injected peripherally in chickens decreases food intake, but because of the delay in gastric emptying related to the crop and gizzard, it may be of minor importance. Possible roles for brain CCK have been suggested because CCK injected into the cerebrospinal fluid (CSF) decreases feeding in all three species. In sheep, food intake was stimulated by sequestration of endogenous CCK in CSF with specific CCK antibodies, which suggests a physiological role for brain CCK controlling food intake in this species. Opioid peptides increased feeding in sheep after i.v. and CSF injections. Only peripheral, and not CSF, injections of naloxone, a specific opiate antagonist, decreased feeding and blocked both peripheral and central opioid peptide-stimulated feeding. The balance of CCK and the opioid peptide activity in either the central nervous system or the periphery appears important in the control of feeding, but specific peptide functions and sites of action probably vary among species.
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Papers by MaryAnne DellaFera