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).

A dietary phytochemical blend prevents liver damage associated with adipose tissue mobilization in ovariectomized rats.

Objective: Menopausal reduction in estrogen causes increased adipose accumulation, leading many to turn to dietary supplements to prevent and treat such changes. Enhanced adipose mobilization stimulated by some supplements can increase the risk of non-alcoholic fatty liver disease (NAFLD). Cytoprotective and anti-obesity compounds may prevent the lipotoxicity associated with mobilization.

Acute exposure to high-fat diets increases hepatic expression of genes related to cell repair and remodeling in female rats.

High-fat diets (HFD) promote the development of both obesity and fatty liver disease through the up-regulation of hepatic lipogenesis. Insulin resistance, a hallmark of both conditions, causes dysfunctional fuel partitioning and increases in lipogenesis. Recent work has demonstrated that systemic insulin resistance occurs in as little as the first 72 hours of an HFD, suggesting the potential for hepatic disruption with HFD at this time point.

The Mediation of Hepatic Lipogenesis Through Estrogens.

Estrogens have been shown to protect against various diseases and disastrous metabolic consequences of poor diets. Although a large body of research demonstrates estrogen's ability to control food intake, adipogenesis, and oxidative stress, research regarding the effects of estrogens on hepatic lipogenesis, steatosis, and non-alcoholic fatty liver disease is only now accumulating. Estrogen deficiency in both human and rodent models directly results in the upregulation of hepatic lipogenic signaling - in both serum and hepatic triglyceride content - which leads to the development of fatty liver.

Adenovirus 36, adiposity, and bone strength in late-adolescent females.

Adenovirus 36 (Ad36) is the only adenovirus to date that has been linked with obesity in humans. Our previous studies in late-adolescent females suggest that excess weight in the form of fat mass is associated with lower cortical bone strength. The purpose of this study was to assess the relationship between Ad36-specific antibodies, adiposity, and bone strength in our sample of late-adolescent females.

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.

Emerging role of apelin as a therapeutic target in cancer: a patent review.

Since tumors cannot grow or spread without forming new blood vessels, inhibiting angiogenesis is an excellent approach for the treatment of cancer. Further, inhibitors of angiogenesis have mild side effects since they act on endothelial cells, which eliminate the possibility of developing resistance or tolerance in tumor cells, unlike that seen with chemotherapy drugs. The anti-vascular endothelial growth factor (VEGF) monoclonal antibody bevacizumab acts by preventing new blood vessel formation in solid tumors and is approved by FDA to treat colorectal, lung, breast, glioblastoma and kidney cancers.

Synergism between resveratrol and other phytochemicals: implications for obesity and osteoporosis.

Resveratrol, a phytoalexin, has gained much attention recently due to its effects on sirtuins. While the anti-cancer properties of resveratrol have been extensively investigated, the anti-adipogenic and osteogenic effects of resveratrol are also gaining considerable interest. The finding that resveratrol supplementation mimics caloric restriction prompted researchers to study the effects of resveratrol on lipid metabolism.

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.

Novel molecular targets for prevention of obesity and osteoporosis.

Evidence from both epidemiological studies and basic research suggests that obesity and osteoporosis are interrelated. Though there is an increase in the prevalence of these disorders, a limited number of treatments are available, one of the reasons being the complexity of the pathways involved and difficulty in identifying a single molecular target. Due to adverse effects of pharmaceuticals, intake of herbal drugs by patients without a physician's recommendation is increasing globally.

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.

Phytochemicals and adipogenesis.

Obesity is an increasing health problem all over the world. Phytochemicals are potential agents to inhibit differentiation of preadipocytes, stimulate lipolysis, and induce apoptosis of existing adipocytes, thereby reducing the amount of adipose tissue. Flavonoids and stilbenoids represent the most researched groups of phytochemicals with regards to their effect on adipogenesis, but there are also a number of in vitro and in vivo studies with phenolic acids, alkaloids, and vitamins, as well as other plant compounds.

Leptin modulated changes in adipose tissue protein expression in ob/ob mice.

Comparative proteomic analyses were performed in adipose tissue of leptin-deficient ob/ob mice treated with leptin or control buffer in order to identify the protein expression changes as the potential targets of leptin. Mice were treated with either phosphate-buffered saline (control) or 10 µg/day leptin for 14 days via subcutaneous osmotic minipumps. Total protein from white adipose tissue was extracted and labeled with different fluorescent cyanine dyes for analysis by two-dimensional difference gel electrophoresis (DIGE).

Effect of clenbuterol on apoptosis, adipogenesis, and lipolysis in adipocytes.

Clenbuterol, a beta(2)-adrenergic receptor (beta(2)-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 beta-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.

Maternal high fat feeding and gestational dietary restriction: effects on offspring body weight, food intake and hypothalamic gene expression over three generations in mice.

Excessive gestational weight gain and maternal obesity have both been associated with increased incidence of obesity and metabolic disorder in offspring in both humans and animal models. The objectives of this study were to determine (1) whether mild gestational food restriction during the third trimester (GFR) would alter food intake and growth parameters of offspring, (2) whether effects of GFR depended on diet (high fat [HF] vs chow), (3) whether effects of excessive gestational weight gain (WG) would become magnified across generations, and (4) whether diet and GFR would alter hypothalamic gene expression in adult offspring. Three generations of female C57BL/6 mice were fed chow or HF diet, mated at 11 weeks of age and assigned to ad libitum feeding or 25% GFR.

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.

Octanoate and decanoate induce apoptosis in 3T3-L1 adipocytes.

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.

Anti-obesity effects of xanthohumol plus guggulsterone in 3T3-L1 adipocytes.

Xanthohumol (XN) and guggulsterone (GS) have each been shown to inhibit adipogenesis and induce apoptosis in adipocytes. In the present study effects of the combination of XN + GS on 3T3-L1 adipocyte apoptosis and adipogenesis were investigated. Mature adipocytes were treated with XN and GS individually and in combination.

Combined effects of genistein, quercetin, and resveratrol in human and 3T3-L1 adipocytes.

The natural compounds genistein (G), quercetin (Q), and resveratrol (R) have been reported to each exhibit anti-adipogenic activities in adipocytes and antiproliferative and pro-apoptotic activities in several cell types. We studied the combined effects of G, Q, and R on adipogenesis and apoptosis in primary human adipocytes (HAs) and 3T3-L1 murine adipocyte (MAs). Combined treatment with 6.

Ajoene exerts potent effects in 3T3-L1 adipocytes by inhibiting adipogenesis and inducing apoptosis.

This paper describes effects of several sulfur-containing compounds from garlic on the cell viability, apoptosis and adipogenesis in 3T3-L1 adipocytes. In both preadipocytes and mature adipocytes, 100 and 200 microM ajoene significantly decreased cell viability and increased apoptosis. The effect on apoptosis was further confirmed with Hoechst staining.

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.

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.

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.

Resveratrol induces apoptosis and inhibits adipogenesis in 3T3-L1 adipocytes.

Resveratrol, a phytoallexin, has recently been reported to slow aging by acting as a sirtuin activator. Resveratrol also has a wide range of pharmacological effects on adipocytes. In this study, we investigated the effects of resveratrol on adipogenesis and apoptosis using 3T3-L1 cells.

Genistein inhibits differentiation of primary human adipocytes.

Genistein, a major soy isoflavone, has been reported to exhibit antiadipogenic and proapoptotic potential in vivo and in vitro. It is also a phytoestrogen which has high affinity to estrogen receptor beta. In this study, we determined the effect of genistein on adipogenesis and estrogen receptor (ER) alpha and beta expression during differentiation in primary human preadipocytes.