Simultaneous Application of High-Intensity Focused Electromagnetic and Synchronized Radiofrequency for Fat Disruption: Histological and Electron Microscopy Porcine Model Study.

BACKGROUND: Radiofrequency (RF) and high-intensity focused electromagnetic (HIFEM) technologies are used for noninvasive body shaping as standalone modalities. OBJECTIVE: To examine the effects of novel synchronized RF and HIFEM on subcutaneous adipose tissue in a porcine animal model. MATERIALS AND METHODS: Seven large white pigs aged 6 months received 3 abdominal treatments of simultaneous application of synchronized RF and HIFEM (30 minutes, once per week). Punch biopsies of treated and control subcutaneous tissue were collected at the baseline, 4 days, 2 weeks, 1 month, and 2 months. Specimens were examined by light and scanning electron microscopy. Adipocyte volume was analyzed. Fat tissue temperature was measured in situ (fiber optic probes) and superficially (thermal imager). RESULTS: Fat layer was heated to temperatures of 42 to 45°C. Signs of fat apoptosis (shape alternations and pyknotic nuclei) appeared at day 4 and peaked between 2 weeks and 1 month. Adipocyte volume decreased significantly (p < .001) by 31.1% at 2 weeks, 1 month (-23.6%), and 2 months (-22.0%). Control samples showed healthy adipocytes. Scanning electron microscopy micrographs corroborated histology findings, showing flattened, volume-depleted and disrupted adipocytes. CONCLUSION: Synchronized RF with HIFEM procedure resulted in a significant and sustained fat reduction with no adverse events.

Comparative Effect between Sardine Oil and Fish Oil Rich in Omega-3 Fatty Acids on Hypertension and the Membrane Composition of Adipocytes in SHR Rats.

Omega-3 polyunsaturated fatty acids, have an important role in reducing hypertriglyceridemia, these acids decrease the mortality for Coronary Heart Disease. Very important is the relationship between fatty acid biosynthesis and distribution in organs and tissues involved in insulin resistance and hypertension due to its role in the production of vasoactive eicosanoids and their effects on insulin sensitivity; which is estimated with the HOMA-IR index, which relates the physiological and metabolic behavior of glucose and insulin in the body. The aim of this project was to compare the effect of sardine oil and omega-3 oils rich in polyunsaturated fatty acids: EPA (≈30%) and DHA (≈50%) administered for 6 to 8 wk respectively; on the lipid composition of the plasma membrane of epididymal adipocytes in spontaneously hypertensive rats (SHR) and their relation to obesity, insulin resistance and hypertension. The administration of omega-3 enriched oil significantly decreased the HOMA criteria as an insulin resistance indicator compared to the sardine oil.

Chenopodium ambrosioides L. extract prevents bone loss

ABSTRACT PURPOSE: To evaluate the effect of the Chenopodium ambrosioides L (mastruz) extract for preventing bone loss and bone metabolism in ovariectomized rats. METHODS: Twelve rats were subjected to bilateral ovariectomy for inducing osteoporosis. After surgery, they were divided into two groups: Ovariectomy-control group (G1, n=6), receiving 0.5 ml distilled water by gavage for 30 days, and Ovariectomy plus mastruz group (G2, n=6), receiving 0.5 ml of the hydroalcoholic extract of mastruz at 10% concentration (50mg) daily, for the same period. Then, the blood of the animals was collected for further biochemical analysis (liver function) and tibia and liver were removed for histological and histomorphometric analyses. RESULTS: The cortical bone was significantly larger in the G2 than G1, whereas G1 presented the highest amount of adipocytes in the bone marrow (p<0.05). The blood levels of aspartate aminotransferase, triglycerides and cholesterol were significantly higher, whereas globulin and lactate dehydrogenase were smaller in G2 than G1. CONCLUSION: The hydroalcoholic extract of mastruz has effects on bone metabolism by changing blood proteins and enzymes and preventing both bone loss and the substitution of bone marrow cells by.

Chenopodium ambrosioides L. extract prevents bone loss.

PURPOSE: To evaluate the effect of the Chenopodium ambrosioides L (mastruz) extract for preventing bone loss and bone metabolism in ovariectomized rats. METHODS: Twelve rats were subjected to bilateral ovariectomy for inducing osteoporosis. After surgery, they were divided into two groups: Ovariectomy-control group (G1, n=6), receiving 0.5 ml distilled water by gavage for 30 days, and Ovariectomy plus mastruz group (G2, n=6), receiving 0.5 ml of the hydroalcoholic extract of mastruz at 10% concentration (50mg) daily, for the same period. Then, the blood of the animals was collected for further biochemical analysis (liver function) and tibia and liver were removed for histological and histomorphometric analyses. RESULTS: The cortical bone was significantly larger in the G2 than G1, whereas G1 presented the highest amount of adipocytes in the bone marrow (p<0.05). The blood levels of aspartate aminotransferase, triglycerides and cholesterol were significantly higher, whereas globulin and lactate dehydrogenase were smaller in G2 than G1. CONCLUSION: The hydroalcoholic extract of mastruz has effects on bone metabolism by changing blood proteins and enzymes and preventing both bone loss and the substitution of bone marrow cells by.

Mango fruit peel and flesh extracts affect adipogenesis in 3T3-L1 cells.

Obesity is associated with many chronic disease states, such as diabetes mellitus, coronary disease and certain cancers, including those of the breast and colon. There is a growing body of evidence that links phytochemicals with the inhibition of adipogenesis and protection against obesity. Mangoes (Mangifera indica L.) are tropical fruits that are rich in a diverse array of bioactive phytochemicals. In this study, methanol extracts of peel and flesh from three archetypal mango cultivars; Irwin, Nam Doc Mai and Kensington Pride, were assessed for their effects on a 3T3-L1 pre-adipocyte cell line model of adipogenesis. High content imaging was used to assess: lipid droplets per cell, lipid droplet area per cell, lipid droplet integrated intensity, nuclei count and nuclear area per cell. Mango flesh extracts from the three cultivars did not inhibit adipogenesis; peel extracts from both Irwin and Nam Doc Mai, however, did so with the Nam Doc Mai extract most potent at inhibiting adipogenesis. Peel extract from Kensington Pride promoted adipogenesis. The inhibition of adipogenesis by Irwin (100 µg mL(-1)) and Nam Doc Mai peel extracts (50 and 100 µg mL(-1)) was associated with an increase in the average nuclear area per cell; similar effects were seen with resveratrol, suggesting that these extracts may act through pathways similar to resveratrol. These results suggest that differences in the phytochemical composition between mango cultivars may influence their effectiveness in inhibiting adipogenesis, and points to mango fruit peel as a potential source of nutraceuticals.

Overexpression of a short human seipin/BSCL2 isoform in mouse adipose tissue results in mild lipodystrophy.

Berardinelli-Seip congenital lipodystrophy type 2 (BSCL2) is a recessive disorder characterized by an almost complete loss of adipose tissue, insulin resistance, and fatty liver. BSCL2 is caused by loss-of-function mutations in the BSCL2/seipin gene, which encodes seipin. The essential role for seipin in adipogenesis has recently been established both in vitro and in vivo. However, seipin is highly upregulated at later stages of adipocyte development, and its role in mature adipocytes remains to be elucidated. We therefore generated transgenic mice overexpressing a short isoform of human BSCL2 gene (encoding 398 amino acids) using the adipocyte-specific aP2 promoter. The transgenic mice produced ∼150% more seipin than littermate controls in white adipose tissue. Surprisingly, the increased expression of seipin markedly reduced the mass of white adipose tissue and the size of adipocytes and lipid droplets. This may be due in part to elevated lipolysis rates in the transgenic mice. Moreover, there was a nearly 50% increase in the triacylglycerol content of transgenic liver. These results suggest that seipin promotes the differentiation of preadipocytes but may inhibit lipid storage in mature adipocytes.

Dissociation of the insulin receptor from caveolae during TNFα-induced insulin resistance and its recovery by D-PDMP.

Previously, we demonstrated that an inhibitor of ganglioside biosynthesis, d-PDMP, could restore impaired insulin signaling in tumor necrosis factor α (TNFα)-treated adipocytes by blocking the increase of GM3 ganglioside. Here, we analyzed the interaction between insulin receptor (IR) and GM3 in the plasma membranes using immunoelectron microscopy. In normal adipocytes, most GM3 molecules localized at planar and non-caveolar regions. Approximately 19% of IR molecules were detected in caveolar regions. The relative ratio of IRs associated with caveolae in TNFα-treated adipocytes was decreased to one-fifth of that in normal adipocytes, but this decrease was restored by d-PDMP. Thus, we could obtain direct evidence that insulin resistance is a membrane microdomain disorder caused by aberrant expression of ganglioside.

TNF-alpha induces mitochondrial dysfunction in 3T3-L1 adipocytes.

TNF-alpha was the first proinflammatory cytokine identified linking obesity, insulin resistance and chronic inflammation. However, the mechanism of TNF-alpha in the etiology of insulin resistance is still far from clear. Because the mitochondria play an important role in energy metabolism, we investigated whether mitochondrial dysfunction is involved in pathogenesis of TNF-alpha-mediated insulin resistance. First, a fully differentiated insulin-resistant 3T3-L1 adipocyte model was established by incubating with 4 ng/ml TNF-alpha for 4 d, and then the mitochondrial morphology and functions were observed. TNF-alpha treatment induced pronounced morphological changes in the mitochondria, which became smaller and condensed, and some appeared hollow and absent of cristae. Mitochondrial dynamics changes were observed as increased mitofusion protein mfn1 and mitofission protein Drp1 levels compared with controls. No obvious effects on mitochondrial biogenesis were found. PGC-1alpha levels decreased, but no significant changes were found in mtTFA mRNA expression, NRF1mRNA expression and mitochondrial DNA (mtDNA). TNFalpha treatment also led to decreased mitochondrial membrane potential and reduced production of intracellular ATP, as well as accumulation of significant amounts of reactive oxygen species (ROS). Further research is required to determine if mitochondrial dysfunction is involved in the inflammatory mechanism of insulin resistance and may be a potential target for the treatment of insulin resistance.

Olanzapine increases cell mitotic activity and oligodendrocyte-lineage cells in the hypothalamus.

Weight gain is increasingly recognized as an unwanted side effect of atypical antipsychotic drugs. To explore the mechanisms underlying this side effect, we examined the effects of olanzapine, an atypical antipsychotic drug, on cellular proliferation and differentiation in the adult mouse hypothalamus. A 6-week treatment with olanzapine resulted in a significant increase in body weight. The sizes and numbers of olanzapine-treated mouse adipocytes were significantly larger than those of control mice. No significant differences were observed in the levels of blood insulin, cholesterol, triglyceride, leptin, and ghrelin among olanzapine-, haloperidol-treated and control mice with an exception that adiponectin was significantly higher in olanzapine group than control group. Body temperature and the level of uncoupling protein 2 were also comparable between the olanzapine-treated and control groups. We found that the treatment increased BrdU-incorporating cell numbers in the hypothalamus, while the same regimen with haloperidol or control had little effect on cellular proliferation. Double-labeling immunohistochemistry revealed that the majority of the BrdU-positive cells were also Olig2- or APC-positive, indicating that oligodendrocyte-lineage cells were generated in response to olanzapine treatment. Enhancement of hypothalamic cellular proliferation after intracerebroventricular infusion of cytosine arabinoside coincided with elevated food intake and weight gain. These findings suggest a possible link between gliogenesis in the hypothalamus and weight gain following olanzapine treatment.

Hypolipidemic and body fat-lowering effects of Fatclean in rats fed a high-fat diet.

The body fat-lowering and hypolipidemic effects of a Fatclean formula were examined in Sprague-Dawley rats fed a high-fat diet. Animals were given a normal control (NC) diet or a 15% high-fat (HF) diet with or without Fatclean (5%, wt/wt) supplement for 6 weeks. Fatclean formula contained phenolic compounds (14.3mg/g) and other functional compounds. Fatclean formula significantly lowered final body weights and visceral fat-pads weights, plasma total cholesterol (TC) and triglyceride (TG) concentrations, hepatic cholesterol and triglyceride levels, and hepatic hydroxyl-3-methylglutaryl-coenzyme A reductase (HMG-CoA) and acyl-coenzyme A:cholesterol acyltransferase (ACAT) activities compared to the HF group. Furthermore, adipocytic lipoprotein lipase (LPL) activity was also significantly elevated in the Fatclean group than in the HF group. The high-density lipoprotein-cholesterol/total-cholesterol (HDL-C/Total-C) ratio and atherogenic index (AI) were significantly improved in the Fatclean group than in the HF group. The accumulation of hepatic lipid droplets and the epididymal white adipocyte size were diminished in the Fatclean group than in the HF group. Accordingly, Fatclean seemed to be beneficial for the reduction of body weight and/or body fat and its hyperlipidemic property was highly active for enhancing the plasma lipids profile.

Effect of low-level laser therapy on abdominal adipocytes before lipoplasty procedures.

Low-level laser therapy is a new subspecialty for the medical application of lasers that provides therapeutic rather than surgical outcomes for many medical indications. Recently, low-level laser therapy was reported to "liquefy" or release stored fat in adipocytes by the opening of specialized yet not identified cell membrane-associated pores after a brief treatment. Currently, low-level laser therapy is a U.S. Food and Drug Administration-approved technology for improving pain alleviation. To explore these data further, a series of in vitro studies on human preadipocytes and institutional animal care and use committee-approved protocols in a porcine Yucatan model and an institutional review board-approved clinical study were performed. Using a 635-nm low-level laser of 1.0 J/cm supplied to the authors by the vendor, these studies were designed to determine whether alteration in adipocyte structure or function was modulated after low-level laser therapy. Cultured human preadipocytes after 60 minutes of laser therapy did not change appearance compared with nonirradiated control cells. In the porcine model, low-level laser therapy (30 minutes) was compared with traditional lipoplasty (suction-assisted lipoplasty) and ultrasound-assisted lipoplasty. From histologic and scanning electron microscopic evaluations of the lipoaspirates, no differences were observed between low-level laser therapy-derived and suction-assisted lipoplasty-derived specimens. Using exposure times of 0, 15, 30, and 60 minutes in the presence or absence of superwet wetting solution and in the absence of lipoplasty, total energy values of 0.9 mW were delivered to tissue samples at three increasing depths from each experimental site. No histologic tissue changes or specifically in adipocyte structure were observed at any depth with the longest low-level laser therapy (60 minutes with superwet fluid). Three subjects undergoing large-volume lipoplasty were exposed to superwet wetting fluid infiltration 14 minutes before and 12 minutes after, according to vendor instructions. Tissue samples from infiltrated areas were collected before suction-assisted lipoplasty and lipoaspirates from suction-assisted lipoplasty. No consistent observations of adipocyte disruptions were observed in the histologic or scanning electron microscopy photographs. These data do not support the belief that low-level laser therapy treatment before lipoplasty procedures disrupts tissue adipocyte structure.

Regulation of glucose transport and transporter 4 (GLUT-4) in muscle and adipocytes of sucrose-fed rats: effects of N-3 poly- and monounsaturated fatty acids.

The goal of this study was to compare the short-term effects of dietary n-3 polyunsaturated (fish oil) and monounsaturated (olive oil) fatty acids on glucose transport, plasma glucose and lipid controls in a dietary insulin resistance model using sucrose-fed rats. The underlying cellular and molecular mechanisms were also determined in the muscle and adipose tissue. Male Sprague-Dawley rats (5 weeks old) were randomized for diets containing 57.5 % (w/w) sucrose and 14 % lipids as either fish oil (SF), olive oil (SO) or a mixture of standard oils (SC) for 3 weeks. A fourth control group (C) was fed a diet containing 57.5 % starch and 14 % standard oils. After three weeks on the diet, body weight was comparable in the four groups. The sucrose-fed rats were hyperglycemic and hyperinsulinemic in response to glucose load. The presence of fish oil in the sucrose diet prevented sucrose-induced hyperinsulinemia and hypertriglyceridemia, but had no effect on plasma glucose levels. Insulin-stimulated glucose transport in adipocytes increased after feeding with fish oil (p < 0.005). These modifications were associated with increased Glut-4 protein (p < 0.05) and mRNA levels in adipocytes. In the muscle, no effect was found on Glut-4 protein levels. Olive oil, however, could not bring about any improvement in plasma insulin, plasma lipids or Glut-4 protein levels. We therefore conclude that the presence of fish oil, in contrast to olive oil, prevents insulin resistance and hypertriglyceridemia in rats on a sucrose diet, and restores Glut-4 protein quantity in adipocytes but not in muscle at basal levels. Dietary regulation of Glut-4 proteins appears to be tissue specific and might depend on insulin stimulation and/or duration of dietary interventions.

Proliferation and differentiation of stromal-vascular cells in primary culture differ between neonatal pigs consuming maternal or formula milk.

Proliferation and differentiation of preadipocytes from 7-d-old pigs consuming maternal or formula milk were examined in primary culture of stromal-vascular (s-v) cells derived from subcutaneous adipose tissue. Unsuckled pigs were bottle-fed isoenergetically with colostrum and then sow's milk (SM) or with formula milk alone (F) from birth to 7 d. Isolated cells were exposed to serum-supplemented medium and serum-free medium to determine proliferation and differentiation, respectively. Proliferation estimated between d 3 and 4 of culture was higher (P<0.05) in cells from F than SM pigs. In addition, the number of s-v cells isolated from 1 g of adipose tissue was higher (P<0.01) in F than SM pigs. Variables assessing differentiation were also affected. The percentage of differentiating cells and lipoprotein lipase (LPL) activity were lower (P<0.05) in F than SM pigs, whereas malic enzyme (ME) activity did not differ significantly between the two groups. In conclusion, formula milk increased the number of s-v cells and their capacity for proliferation, whereas the potential for cell differentiation was lower compared with cells from the maternal milk group. Further studies are required to identify the growth and/or nutritional factors that are implicated in the observed differences and to determine whether subsequent development of adipose tissue is affected.

Dietary (n-3) polyunsaturated fatty acids improve adipocyte insulin action and glucose metabolism in insulin-resistant rats: relation to membrane fatty acids.

To study the effects of dietary fish oil on insulin-stimulated glucose metabolism in adipocytes of insulin-resistant rats (rats fed 50% sucrose and 30% fat), eighteen 5-wk-old Sprague-Dawley rats were fed, for 6 wk, a diet containing 30% fat as either fish oil (FO) or a mixture of vegetable and animal oils [control oils (CO)]. A third reference group was fed a standard diet (62% corn starch and 13% fat). At the end of the 6-wk period, the two experimental groups had comparable plasma glucose concentrations that were higher than that found in the reference group. FO feeding corrected the hyperinsulinemia of the experimental rats (P < 0.05) to reach values in the reference group. Plasma triacylglycerol (P < 0.01) and cholesterol (P < 0.001) concentrations were also lower in rats fed FO than in those fed CO. The body weights of FO-fed rats were similar to that of CO-fed rats, but epididymal adipose tissue weight was lower (P < 0.01). Adipocytes of FO-fed rats, compared with those of CO-fed rats, had high insulin-stimulated glucose transport (P < 0.05), oxidation (P < 0.001) and incorporation into total lipids (P < 0.05). The incorporation of (n-3) polyunsaturated fatty acids in adipocyte membrane phospholipids was higher in FO-fed rats than in those fed CO (P < 0.0001). Insulin action was positively correlated with the fatty acid unsaturation index in membrane phospholipids. Thus dietary fish oil has beneficial effects on insulinemia, plasma lipids and insulin-stimulated glucose metabolism in insulin-resistant slightly diabetic rats.