The Impact of Cat Fostering on Older Adult Well-Being and Loneliness: A Feasibility Study.

OBJECTIVES: This feasibility study explored the impact of fostering a shelter cat on loneliness and well-being in older adults living alone without a pet. The study also examined the effect of cat fostering on older adults' interest in cat adoption when perceived barriers to adoption were removed. METHODS: A total of 29 adults (age ≥60) were paired with a cat and asked to foster for a minimum of 4 months (with an option to adopt). Participants completed surveys before placement with cats, with a follow-up at 1 and 4 months postplacement and 12 months if they adopted their cat. The survey included scales of loneliness, physical and mental health, self-efficacy, positive and negative affect, and comfort from a companion animal. Scores were compared across time using a Multivariable Linear Mixed Model. RESULTS: A total of 23 of 29 (79.3%) participants remained in the study for at least 4 months, and a majority (95.7%) adopted their cat. Differences in marginal means (adjusted for physical health) showed a significant improvement in loneliness from baseline to 4 months (p = .029). A similar 4-month improvement that approached statistical significance (adjusted p = .079) was observed for mental health. No other scales showed statistically significant changes across time. DISCUSSION: Fostering a shelter cat with the option for adoption may be an effective solution for alleviating loneliness and improving mental health in older adults. Interest in adopting foster cats was high when perceived barriers to adoption were removed.

Synergistic Phytochemicals Fail to Protect Against Ovariectomy Induced Bone Loss in Rats.

Menopause induces a loss of bone as a result of estrogen deficiency. Despite pharmaceutical options for the treatment of osteopenia and osteoporosis, many aging women use dietary supplements with estrogenic activity to prevent bone loss and other menopausal-related symptoms. Such supplements are yet to be tested for efficacy against a Food and Drug Administration (FDA) approved medication for menopausal bone loss such as zoledronic acid (ZA). The postmenopausal rat model was used to investigate the efficacy of various synergistic phytochemical blends mixed into the diet for 16 weeks. Retired-breeder, Fischer 344 rats were randomly assigned to sham or ovariectomy surgery and 4 treatment groups: ZA; genistein supplementation; and a low dose and high dose blend of genistein, resveratrol, and quercetin. Ovariectomy resulted in a loss of both trabecular and cortical bone which was prevented with ZA. The phytochemical blends tested were unable to reverse these losses. Despite the lack of effectiveness in preventing bone loss, a significant dose-response trend was observed in the phytochemical-rich diets in bone adipocyte number compared to ovariectomized control rats. Data from this study indicate that estrogenic phytochemicals are not as efficacious as ZA in preventing menopausal-related bone loss but may have beneficial effects on bone marrow adiposity in rats.

A Twelve-Week Lifestyle Program to Improve Cardiometabolic, Behavioral, and Psychological Health in Hispanic Children and Adolescents.

OBJECTIVES: To examine the effectiveness of a 12-week lifestyle program on cardiometabolic, behavioral, and psychological outcomes among overweight Hispanic children and adolescents. DESIGN: A case series study with pre- and post-test analyses. Subjects/Settings/Location: A convenience sample of high-risk pediatric primary care patients (n = 22; 6 girls, 16 boys; M age = 11.73 ± 1.39 years) and their guardians in the Southeast United States. INTERVENTION: Twice per week 60 min (total of 24 h) of moderate-to-vigorous intensity boxing exercise training, 12 h of nutrition education for guardians, and a 30-min pediatrician appointment. OUTCOME MEASURES: Cardiometabolic (height [m], weight [kg], waist circumference [cm], body-mass index [BMI], BMI-z, BMI%, cholesterol [mg/dL], triglycerides [mg/dL], glucose [mg/dL], and low-density lipoprotein and high-density lipoprotein cholesterol [mg/dL]), behavioral (objective free time physical activity [PA] and sedentary time [min/day]), and psychological (self-determined exercise motivation) outcomes were measured/calculated, and paired-samples t-tests were conducted. RESULTS: A significant reduction was observed in waist circumference t(17) = -2.57, p = 0.020, d = 0.64; BMI% t(15) = -2.53, p = 0.023, d = 0.20; fasting glucose t(15) = -6.43, p < 0.001, d = 1.67; and amotivation (-) t(17) = -2.29, p = 0.036, d = 0.64; whereas a significant increase was identified in moderate t(10) = 4.01, p = 0.002, d = 1.23 and vigorous t(10) = 3.41, p = 0.007, d = 1.07 intensity PA; intrinsic motivation t(17) = 2.71, p = 0.015, d = 0.38; and introjected regulation t(17) = 2.74, p = 0.014, d = 0.64. CONCLUSIONS: A 12-week lifestyle program can be effective in improving selected health markers among overweight Hispanic children and adolescents. The positive changes in fasting glucose, BMI, and waist suggest that the participants are currently at lower risk for both type 2 diabetes and cardiovascular disease as a result of the Confidence, Ownership, Responsibility, and Exercise program.

A 72-hour high fat diet increases transcript levels of the neuropeptide galanin in the dorsal hippocampus of the rat.

BACKGROUND: Recent evidence identifies the hippocampus, a brain structure commonly associated with learning and memory, as key to the regulation of food intake and the development and consequences of obesity. Intake of a high fat diet (HFD) results in altered consumptive behavior, hippocampal damage, and cognitive deficits. While many studies report the effects of HFD after chronic consumption and in the instance of obesity, few examine the events that occur following acute HFD consumption. In this study, male rats were fed either a control diet (10% fat by kcal) or HFD (45% fat by kcal) for 72 h. At the end of the 72-h period, serum and tissues were collected and weighed. Brains were rapidly frozen or formalin-fixed in preparation for qRT-PCR or immunohistochemistry, respectively. RESULTS: Acute intake of HFD resulted in higher serum levels of leptin and cholesterol, with no significant changes in final body weight or adipose tissue mass. In the dorsal hippocampus, transcription of the neuroprotective peptide galanin was significantly upregulated along with a trend for an increase in brain-derived neurotrophic factor and histone deacetylase 2 in the rats fed HFD. In the ventral hippocampus, there was a significant increase in histone deacetylase 4 and a decrease in galanin receptor 1 in this group. Results from immunohistochemistry validate strong presence of the galanin peptide in the CA1/CA2 region of the dorsal hippocampus. CONCLUSIONS: These results provide evidence for a distinct response in specific functional regions of the hippocampus following acute HFD intake.

Preventing bone loss and weight gain with combinations of vitamin D and phytochemicals.

Vitamin D and certain natural compounds have been shown to regulate both lipid metabolism and bone formation. Treatments that prevent or reverse age-related increase in bone marrow adiposity could both increase new bone formation and inhibit bone destruction. We tested the hypothesis that dietary supplementation with combinations of vitamin D and phytochemicals inhibits bone loss and decreases adiposity to a greater extent than control or vitamin D-alone diets. Aged ovariectomized female rats (12 months old, n=50, initial body weight=240 g) were given control (AIN-93M diet), vitamin D (2,400 IU/kg), or vitamin D plus resveratrol (16, 80, or 400 mg/kg of diet [low, medium, and high dose, respectively]), quercetin (80, 400, or 2,000 mg/kg of diet), and genistein (64, 256, or 1,040 mg/kg of diet) for 8 weeks. The high-dose treatment (vitamin D+400 mg/kg resveratrol+2,000 mg/kg quercetin+1,040 mg/kg genistein) reduced body weight gain (P<.05) and the fat pad weights (P<.05). This treatment also increased the serum concentration of insulin-like growth factor-1 (P<.05) and the bone mineral content of the femur. Micro-computed tomography and histomorphometric analyses indicated that the high-dose treatment prevented loss of trabecular bone (P<.05) and reduced marrow adipocytes (P<.001) and osteoclasts (P<.05) compared with the control and vitamin D alone (P<.05). We conclude that aged ovariectomized female rats supplemented with vitamin D combined with genistein, quercetin, and resveratrol had improved bone mineral density and reduced body weight gain and a significant decrease in bone marrow adipocytes. The synergistic effects of a combination of phytochemicals with vitamin D may be effective in reducing bone loss and weight gain after menopause.

Central (ICV) leptin injection increases bone formation, bone mineral density, muscle mass, serum IGF-1, and the expression of osteogenic genes in leptin-deficient ob/ob mice.

Both central and peripheral leptin administrations reduce body weight, food intake, and adiposity in ob/ob mice. In this study we compared effects of intracerebroventricular (ICV) and subcutaneous (SC) administration of leptin on bone metabolism in the appendicular and axial skeleton and adipose tissue gene expression and determined the effects of ICV leptin on bone marrow gene expression in ob/ob mice. In experiment 1, leptin (1.5 or 0.38 µg/d) or control was continuously injected ICV for 12 days. Gene expression analysis of femoral bone marrow stromal cells showed that expression of genes associated with osteogenesis was increased after ICV injection, whereas those associated with osteoclastogenesis, adipogenesis, and adipocyte lipid storage were decreased. In experiment 2, leptin was injected continuously ICV (0.0 or 1.5 µg/d) or SC (0.0 or 10 µg/d) for 12 days. In both experiments, regardless of mode of administration, leptin decreased body weight, food intake, and body fat and increased muscle mass, bone mineral density, bone mineral content, bone area, marrow adipocyte number, and mineral apposition rate. Serum insulin was decreased, whereas serum osteocalcin, insulin-like growth factor 1, osteoprotegerin, pyridinoline, and receptor activator of nuclear factor κB ligand concentrations were increased. In experiment 2, expression of genes in adipose tissue associated with apoptosis, lipid mobilization, insulin sensitivity, and thermogenesis was increased, whereas expression of genes associated with cell differentiation and maturation was decreased regardless of mode of administration. Thus ICV injection of leptin promotes expression of pro-osteogenic factors in bone marrow, leading to enhanced bone formation in ob/ob mice.

Effect of resveratrol on fat mobilization.

Higher levels of body fat are associated with increased risk for development of numerous adverse health conditions. Phytochemicals are potential agents to inhibit differentiation of preadipocytes, stimulate lipolysis, and induce apoptosis of existing adipocytes, thereby reducing adipose tissue mass. Resveratrol decreased adipogenesis and viability in maturing preadipocytes; these effects were mediated not only through down-regulating adipocyte specific transcription factors and enzymes but also by genes that modulate mitochondrial function. Additionally, resveratrol increased lipolysis and reduced lipogenesis in mature adipocytes. In addition, combining resveratrol with other natural products produced synergistic activities from actions on multiple molecular targets in the adipocyte life cycle. Treatment of mice with resveratrol alone was shown to improve resistance to weight gain caused by a high-fat diet. Moreover, dietary supplementation of aged ovariectomized rats with a combination of resveratrol and vitamin D, quercetin, and genistein not only decreased weight gain but also inhibited bone loss. Combining several phytochemicals, including resveratrol, or using them as templates for synthesizing new drugs, provides a large potential for using phytochemicals to target adipocyte adipogenesis, apoptosis, and lipolysis.

Central leptin versus ghrelin: effects on bone marrow adiposity and gene expression.

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.

ICV vs. VMH injection of leptin: comparative effects on hypothalamic gene expression.

Leptin regulates feeding behavior and body weight by binding to its receptors localized in specific areas of the hypothalamus. Leptin injected twice daily for 4 days either into the right ventromedial hypothalamus (VMH) or into the right lateral cerebral ventricle (ICV) and using Real-Time Taqman RT-PCR, mRNA expression levels of selected genes in the arcuate nucleus-median eminence (ARC-ME) complex were quantitatively measured. Expression of selected genes from the ipsi- vs. contralateral VMH areas in rats injected with leptin into the VMH was also compared. VMH injections of leptin increased ARC-ME mRNAs of proopiomelanocortin (POMC), 27.3% (p<0.05); gamma-aminobutyric acid A receptor (GABRD), 89.3% (p<0.01); and thyrotropin-releasing hormone (TRH), 57.7% (p<0.01); and decreased janus kinase 2 (JAK2), 44.4% (p<0.001); suppressor of cytokine signaling 3 (SOCS3), 86.6% (p<0.001); signal transducer and activator of transcription 3 (STAT3), 46.8% (p<0.01); tyrosine hydroxylase (TH), 51.1% (p<0.001); prostaglandin E synthase (PTGES), 96.5% (p<0.001); tumor necrosis factor-alpha (TNF-alpha), 47% (p<0.01); and secretin, 55.4% (p<0.001). Only GABRD, 76.6% (p<0.01) and SCT, 64.9% (p<0.01) were up-regulated in the hypothalamic ARC-ME of rats with ICV leptin injections. VMH injections of leptin induced identical reductions in expression levels of CART, SOCS3, PTGES, and TNF-alpha in both VMH areas; except TH mRNA, whose expression was lowered ipsilaterally. Food intake, body and fat pad weights and serum insulin and leptin were also decreased in rats given leptin through VMH. This study suggests that leptin either unilateral exposure through VMH or bilateral exposure through ICV injections induces divergent ARC-ME gene profiles.

Regulation of adipogenesis by medium-chain fatty acids in the absence of hormonal cocktail.

We report here that octanoate and decanoate, 8-carbon and 10-carbon medium-chain fatty acids (MCFA), decreased adipogenesis in 3T3-L1 preadipocytes when treated with standard hormonal cocktail, but increased adipogenesis in a dose-dependent manner (with decanoate being more effective) when treated with basal media. Addition of dexamethasone to basal medium with either octanoate or decanoate further increased adipogenesis. In order to understand the adipogenic effects of MCFA in the absence of standard hormonal cocktail, postconfluent 3T3-L1 preadipocytes were treated with octanoate or decanoate, and the change in the expression of several adipogenic transcription factors and enzymes was investigated using real-time RT-PCR. Octanoate and decanoate up-regulated the mRNA expression of peroxisome-proliferator-activated receptor (PPAR) gamma, CCAAT/enhancer-binding protein (C/EBP) alpha, fatty-acid-binding protein, sterol-regulatory element binding protein 1c, lipoprotein lipase and hormone-sensitive lipase, and the protein expression of PPARgamma and C/EBPalpha, with decanoate being more effective. Moreover, the PPARgamma antagonist GW9662 inhibited MCFA-induced lipid accumulation by about 50%. Decanoate and octanoate, to a lesser degree, increased lipid accumulation, which was associated with an increase in glycerol-3-phosphate dehydrogenase activity. These results show that octanoate and decanoate may stimulate differentiation of preadipocytes, at least in part, by their influence on the expression of PPARgamma and other adipocyte-specific factors.

Adipose tissue gene expression profiles in ob/ob mice treated with leptin.

Leptin plays a critical role in regulating body weight, lipid metabolism, apoptosis and microvasculature of adipose tissue. To explore multiple signaling pathways of leptin action on adipose tissue, real-time PCR utilizing TaqMan low-density arrays was performed to compare mRNA expression in adipose tissue of ob/ob mice treated with vehicle or leptin (2.5 microg/d or 10 microg/d) for 14 days via subcutaneous osmotic minipumps. Of the 24 target genes selected for characterization, many were differentially expressed between control ob/ob mice and leptin-treated ob/ob mice. Increases in mRNA expression were found for hormone sensitive lipase (HSL), uncoupling protein 2 (UCP2), adrenergic receptor 3 (ADR3), mitofusin 2 (Mfn2), sirtuin 3 (Sirt3), transcription factor sterol regulatory element binding factor 1 (SREBF1), Bcl-2, Bax, Caspase 3, tumor necrosis factor alpha (TNFalpha), adiponectin and angiopoietin 2 (Ang-2). Decreases in expression were found for stearoyl-coenzyme A desaturase 1 (SCD1), fatty acid synthase (FAS), and retinol binding protein 4 (RBP4). There were no changes in expression of transcription factors involved in adipocyte differentiation (C/EBPalpha, PPARalpha, and PPARgamma). These results confirm that alterations in the expression of specific adipose tissue genes including those associated with the promotion of lipid mobilization, energy dissipation, and apoptosis may mediate leptin-induced fat loss in ob/ob mice.

Enhanced inhibition of adipogenesis and induction of apoptosis in 3T3-L1 adipocytes with combinations of resveratrol and quercetin.

Certain flavonoids have been shown to have specific effects on biochemical and metabolic functions of adipocytes. In this study, we investigated the effects of combinations of resveratrol and quercetin on adipogenesis and apoptosis in 3T3-L1 cells. In maturing preadipocytes resveratrol and quercetin at 25 microM individually suppressed intracellular lipid accumulation by 9.4+/-3.9% (p<0.01) and 15.9+/-2.5%, respectively, (p<0.001). The combination of resveratrol and quercetin at the same dose, however, decreased lipid accumulation by 68.6+/-0.7% (p<0.001). In addition, combinations of resveratrol and quercetin at 25 microM significantly decreased the expression of peroxisome proliferators-activated receptor gamma (PPAR gamma) and CCAAT/enhancer-binding protein (C/EBP)alpha, both of which act as key transcription factors. In mature adipocytes resveratrol and quercetin at 100 microM individually decreased viability by 18.1+/-0.6% (p<0.001) and 15.8+/-1% (p<0.001) and increased apoptosis (100 microM) by 120.5+/-8.3% (p<0.001) and 85.3+/-10% (p<0.001) at 48 h, respectively. Combinations of resveratrol and quercetin further decreased viability (73.5+/-0.9%, p<0.001) and increased apoptosis (310.3+/-9.6%, p<0.001) more than single compounds alone. The combination of resveratrol and quercetin at 100 muM increased release of cytochrome c from mitochondria to cytosol and decreased ERK 1/2 phosphorylation. Taken together, our data indicate that combinations of resveratrol and quercetin can exert potential anti-obesity effects by inhibiting differentiation of preadipocytes and inducing apoptosis of mature adipocytes.

ICV leptin effects on spontaneous physical activity and feeding behavior in rats.

Although leptin causes negative energy balance by reducing food intake and increasing energy expenditure, the effect of leptin on spontaneous physical activity (SPA) is not clearly established. To test the hypothesis that leptin enhances SPA in rats, male Sprague-Dawley rats were injected intracerebroventricularly (ICV) with either 10mug of leptin or artificial cerebrospinal fluid (aCSF) before dark onset (12:00h) once daily for 5 successive days. The rats were individually housed in behavioral monitoring cages to measure feeding behavior and SPA throughout the study. Both groups had a diurnal pattern of SPA being low during the light period and high during the dark period. Specifically, there were two peaks of SPA during the dark period, with the first peak taking place around the dark onset and the second occurring approximately 6h towards the light onset. Leptin treatment resulted in a significant increase in SPA whether or not it was expressed in terms of light-dark, daily or diurnal basis. Increased SPA was consistently observed throughout the entire 5-day study in spite of the fact that the rats were consistently eating less and losing body weight. With reduction in weight of fat pads and increase in apoptosis of fat pads but no change in body temperature, leptin decreased size, duration and number of meals without altering eating rate, thereby increasing satiety. Our data show that increased activity is a key determinant in negative energy balance induced by leptin, which cannot be accounted for solely by the leptin-induced food intake reduction.

Gene expression in arcuate nucleus-median eminence of rats treated with leptin or ciliary neurotrophic factor.

Ciliary neurotrophic factor (CNTF) and leptin are cytokine-like% hormones and act on their corresponding receptors in the hypothalamic arcuate nucleus (ARC). The present study was designed to assess effects of intracerebroventricular (ICV) injection of leptin and CNTF on gene expression in micropunched hypothalamic arcuate nucleus-median eminence (ARC-ME) complex samples from rats. Male Sprague Dawley rats were implanted with lateral cerebroventricular cannulas for administration of control, 10 microg/d leptin or 5 microg/d CNTF for four days. Real-time Taqmantrade mark RT-PCR was used to quantitatively compare the mRNA levels of selected genes in the ARC-ME complex. Leptin and CNTF increased ARC-ME mRNA levels of signal transducer and activator of transcription 3 (STAT3) by 64.5 and 124.7% (p<0.01), suppressor of cytokine signaling 3 (SOCS3) by 258.9 and 1063.9% (p<0.01), cocaine and amphetamine regulated transcript (CART) by 102.7 and 123.1% (p<0.01), and proopiomelanocortin (POMC2) by 374.1 and 264.9% (p<0.01), respectively. Leptin increased growth hormone releasing hormone (GHRH) by 309.9% (p<0.01), while CNTF increased janus kinase 2 (JAK2) mRNA by 31.7% (p<0.01) and decreased gonadotropin releasing hormone 1 (GNRH1) by 59.7% (p<0.01), mitogen activated protein kinase 1 (MAPK1) by 19.4% (p<0.05) and tyrosine hydroxylase (TH) by 74.5% (p<0.05). Significant reduction in daily food intake and body weights by both the treatments was observed. Also, decrease in weights of fat pads was concomitant with lowered serum insulin and leptin levels. Our findings show that leptin and CNTF engage both convergent and divergent pathways involved in feeding, cellular signaling, inflammation, and other related regulatory systems.

Esculetin induces apoptosis and inhibits adipogenesis in 3T3-L1 cells.

OBJECTIVE: To determine the effects of esculetin, a plant phenolic compound with apoptotic activity in cancer cells, on 3T3-L1 adipocyte apoptosis and adipogenesis. RESEARCH METHODS AND PROCEDURES: 3T3-L1 pre-confluent preadipocytes and lipid-filled adipocytes were incubated with esculetin (0 to 800 microM) for up to 48 hours. Viability was determined using the Cell Titer 96 Aqueous One Solution cell proliferation assay; apoptosis was quantified by measurement of single-stranded DNA. Post-confluent preadipocytes were incubated with esculetin for up to 6 days during maturation. Adipogenesis was quantified by measuring lipid content using Nile Red dye; cells were also stained with Oil Red O for visual confirmation of effects on lipid accumulation. RESULTS: In mature adipocytes, esculetin caused a time- and dose-related increase in adipocyte apoptosis and a decrease in viability. Apoptosis was increased after only 6 hours by 400 and 800 microM esculetin (p < 0.05), and after 48 hours, as little as 50 microM esculetin increased apoptosis (p < 0.05). In preadipocytes, apoptosis was detectable only after 48 hours (p < 0.05) with 200 microM esculetin and higher concentrations. However, results of the cell viability assay indicated a reduction in preadipocyte number in a time- and dose-related manner, beginning as early as 6 hours with 400 and 800 microM esculetin (p < 0.05). Esculetin also inhibited adipogenesis of 3T3-L1 preadipocytes. Esculetin-mediated inhibition of adipocyte differentiation occurred during the early, intermediate, and late stages of the differentiation process. In addition, esculetin induced apoptosis during the late stage of differentiation. DISCUSSION: These findings suggest that esculetin can alter fat cell number by direct effects on cell viability, adipogenesis, and apoptosis in 3T3-L1 cells.

Genistein decreases food intake, body weight, and fat pad weight and causes adipose tissue apoptosis in ovariectomized female mice.

Genistein, an isoflavone in soybean products, has estrogenic activity and is used as a natural substitute for estrogen replacement therapy in postmenopausal women. Genistein was also shown to decrease fat pad weight in female mice. The primary objective of this study was to determine the effect of genistein on adipose tissue apoptosis in vitro and in vivo. 3T3-L1 preadipocytes and mature adipocytes were treated with 0, 1, 10, 100, and 400 micromol/L genistein and then assayed for apoptosis, whereas only mature adipocytes were assayed for viability. Mature adipocytes treated with genistein demonstrated a dose-related increase in apoptosis. Ovariectomized female mice (9 mo old) were given 0, 150, or 1,500 mg/kg genistein in the semipurified phytoestrogen-free casein-based diet for 3 wk (n=10). After mice were killed, body composition was determined by dual-energy X-ray absorptiometry analysis, and parametrial (PM), inguinal (ING), and retroperitoneal (RP) fat pads were weighed and assayed for apoptosis (% DNA fragmentation). Genistein (1500 mg/kg) reduced food intake (FI) by 14% (P<0.01) and body weight (BW) by 9% (P<0.01). Body composition was not significantly affected, but PM and ING weights were decreased 22% (P<0.05) and 19% (P<0.07), respectively, by 1,500 mg/kg genistein. Apoptosis in ING fat was increased 290% (P<0.05) by 1,500 mg/kg genistein. These findings show that oral genistein treatment can reduce BW, mobilize body fat, and induce apoptosis of adipose tissue in ovariectomized female mice. Thus, genistein may be useful in treating or preventing increased adiposity after menopause.

Sensitivity of ob/ob mice to leptin-induced adipose tissue apoptosis.

OBJECTIVE: ob/ob mice have increased sensitivity to many of leptin's effects. The primary objective of this experiment was to determine whether ob/ob mice demonstrated increased sensitivity to leptin-induced adipose tissue apoptosis. RESEARCH METHODS AND PROCEDURES: Fifteen-week-old female ob/ob and Ob/? mice received 0 (saline), 2.5, or 10 microg/d leptin for 14 days through subcutaneous (sc) osmotic minipumps. Food intake (FI), body temperature, physical activity, and body weight were measured daily. Body composition and weights and adipose tissue apoptosis (percentage DNA fragmentation) of inguinal, parametrial, and retroperitoneal fat pads were determined at the end of the study. RESULTS: FI decreases were more pronounced in ob/ob. Leptin (10 microg/d) decreased total FI 71% in ob/ob and 34% in Ob/? (p < 0.05). Body weight was decreased by both doses of leptin in ob/ob (p < 0.01) but was unchanged in Ob/?. Leptin increased body temperature in ob/ob but not in Ob/?. Physical activity was increased 400% by 10 microg/d leptin in ob/ob (p < 0.01) but decreased 13% in Ob/? (p < 0.01). Body fat content of ob/ob was reduced by both leptin doses, whereas only 10 microg/d leptin decreased body fat in Ob/?. Fat pad weights were decreased similarly by leptin in both genotypes. However, apoptosis was increased by leptin in all three fat pads in ob/ob, whereas Ob/? showed significant increases only in retroperitoneal. DISCUSSION: ob/ob mice had greater overall sensitivity to leptin. Although ob/ob mice appeared to be more sensitive than Ob/? mice to leptin-induced adipose tissue apoptosis, there were differences among adipose depots in responsiveness to leptin-induced apoptosis.

CART peptide: central mediator of leptin-induced adipose tissue apoptosis?

Because of connections between CART peptide containing neurons and the sympathetic nervous system (SNS) and the possible role of the SNS in leptin-induced adipose apoptosis, CART may act as a downstream effector of leptin-induced adipose apoptosis. Male Sprague-Dawley rats received continuous intracerebroventricular (i.c.v.) infusion for 4 days of either artificial cerebrospinal fluid (aCSF, 12 microl/day), leptin (15 microg/day), or CART55-102 at 2.4 microg/day (CART2.4) or 9.6 microg/day (CART9.6). Food intake (FI) was decreased 10.8% for CART2.4, 41.9% for CART9.6 and 33.4% for leptin (p<0.05). CART9.6 and leptin reduced meal size and meal number. Body weight (BW) was reduced by CART9.6 (14.6%) and leptin (11.6%) (p<0.05), but not by CART2.4. CART9.6 and CART2.4, but not leptin, caused hypothermia, and CART9.6 inhibited physical activity (p<0.05). Epididymal, inguinal and retroperitoneal fat pad weights were reduced (p<0.05) by both CART treatments and leptin; CART9.6 also reduced gastrocnemius muscle weight (18.1%, p<0.05). Leptin, but not CART, increased serum free fatty acid concentrations by 31.1% (p<0.05) and increased adipose apoptosis by 48% (p<0.05). These data show that although leptin and CART55-102 have some similar actions, CART55-102 is probably not a mediator for leptin-induced adipose apoptosis in the brain.

beta-Adrenergic receptor agonists increase apoptosis of adipose tissue in mice.

beta-Adrenergic receptor (beta-AR) agonists increase muscle mass and decrease body fat in rodents and livestock. With oral administration, however, the effects of beta1-AR and beta2-AR can be different, depending on the species tested. We tested the effects of clenbuterol, a beta2-AR agonist, and ractopamine, a beta1/beta2-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+/-3mg and 207+/-20mg, 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 beta-AR in mice, although the mechanism is unknown.