Azaftig stimulates in vitro lipolysis by rodent and human adipocytes

Azaftig is an urinary proteoglycan present in some cancer and AIDS patients experiencing weight loss. Administration of azaftig to mice results in weight loss that is associated with loss of fat depot. So far, very little is known about the mechanism underlying loss of fat depot in mice or weight loss in patients excreting azaftig. Augmentation of lipolysis may be one mechanism that can cause reduction of fat depot. Therefore, the present study was designed to examine the effect of azaftig on lipolysis by adipocytes derived from obese rats and humans. Results show a dose-dependent potentiation of lipolysis by azaftig in both rat and human adipocytes.     

Serum Leptin Concentrations and Weight Gain in Postobese,Postmenopausal Women

Objective : This study was designed to determine if serum leptin concentrations (adjusted for fat mass) after weight loss on a low-calorie diet predict subsequent weight gain. Research Methods and Procedures : Body composition and serum leptin concentrations were determined on 14 moderately obese, postmenopausal, nondiabetic women with a familial predisposition to obesity. Assessments were obtained under tightly controlled metabolic ward conditions of macronutrient intake and weight maintenance both before (obese state) and after a mean weight loss of 12.0 kg to normal body weight (postobese state). Four years later, without intervention, body weight and body composition were reassessed. Results : Weight loss resulted in significant decreases in fat mass (29.7 ± 5.4 vs. 20.3 ± 4.7; kg), body mass index (27.7 ± 1.6 vs. 23.0 ± 1.5; kg/m2), percent body fat (40.7 ± 4.3 vs. 33.1 ± 5.0), and serum leptin concentrations (31.8 ± 16.0 vs. 11.5 ± 5.4; ng/mL). Serum leptin concentrations were positively correlated (p<<0.05) with fat mass in both the obese and postobese states (r = 0.67 and r = 0.56, respectively). However, residual serum leptin concentrations (adjusted for fat mass) in the obese and postobese states were not related to changes in body weight (p<= 0.61 and 0.52), fat mass (p = 0.72 and 0.42), body mass index (p = 0.59 and 0.33), or percent body fat (p = 0.84 and 0.46) over the follow-up period. Discussion : These finding do not support the hypothesis that relatively low concentrations of leptin predict weight regain after weight loss. However, because the number of subjects in this study was limited, further studies are warranted.     

Regulation of lean mass, bone mass, and exercise tolerance by the central melanocortin system

Signaling via the type 4-melanocortin receptor (MC4R) is an important determinant of body weight in mice and humans, where loss of function mutations lead to significant obesity. Humans with mutations in the MC4R experience an increase in lean mass. However, the simultaneous accrual of fat mass in such individuals may contribute to this effect via mechanical loading. We therefore examined the relationship of fat mass and lean mass in mice lacking the type-4 melanocortin receptor (MC4RKO). We demonstrate that MC4RKO mice display increased lean body mass. Further, this is not dependent on changes in adipose mass, as MC4RKO mice possess more lean body mass than diet-induced obese (DIO) wild type mice with equivalent fat mass. To examine potential sources of the increased lean mass in MC4RKO mice, bone mass and strength were examined in MC4RKO mice. Both parameters increase with age in MC4RKO mice, which likely contributes to increases in lean body mass. We functionally characterized the increased lean mass in MC4RKO mice by examining their capacity for treadmill running. MC4R deficiency results in a decrease in exercise performance. No changes in the ratio of oxidative to glycolytic fibers were seen, however MC4RKO mice demonstrate a significantly reduced heart rate, which may underlie their impaired exercise performance. The reduced exercise capacity we report in the MC4RKO mouse has potential clinical ramifications, as efforts to control body weight in humans with melanocortin deficiency may be ineffective due to poor tolerance for physical activity.     

Effects of a hypocaloric,low-carbohydrate diet on weight loss,blood lipids,blood pressure,glucose tolerance,and body composition in free-living overweight women

The purpose of the current study was to examine the effects of a very low-carbohydrate diet on weight loss and biochemical parameters in overweight women. Twenty women completed an 8-week trial that reduced their daily carbohydrate intake from 232 to 71 g (p < 0.05) and reduced energy by 2,644 kJ/day (8,384 to 5,740 kJ, p < 0.001). The average weight loss was 5.0 kg (p < 0.0001), with a net decrease in body mass index of 1.82 kg/m2, a loss of 3.4% body fat (4 kg, p < 0.0001), and a loss of 1.0 kg lean mass (p < 0.05). There were no significant changes in fasting blood glucose, fasting serum insulin, oral glucose tolerance, free or total insulin-like growth factor-1, or total IGFBP-3. Systolicblood pressure decreased by an average of 9.0 mmHg (1 mmHg = 133.322 Pa) (p < 0.01) and diastolic blood pressure decreased by 7 mmHg (p < 0.05). Total cholesterol decreased 1.2 mM (p < 0.001), all of which was accounted for by a decrease in low-density lipoprotein cholesterol (p < 0.001) with no change in high-density lipoprotein cholesterol (baseline, 1.17 mM; week 8, 1.22 mM). Total triacylglycerol decreased 0.6 mM (p < 0.01), and the ratio of triacylglycerol/HDL also significantly decreased (baseline, 1.40; week 8, 0.87; p < 0.001). Serum beta-hydroxybutyrate concentrations rose significantly by week 2 and declined thereafter but remained significantly higher than baseline values for the duration of the intervention. Therefore, carbohydrate restriction to 70 g or less with concomitant energy restriction, without changes in protein or fat consumption, promotes weight loss, and improvements in body composition, blood pressure, and blood lipids without compromising glucose tolerance in moderately overweight women.     

Orlistat 60 mg reduces visceral adipose tissue: a 24-week randomized, placebo-controlled, multicenter trial

It is well established that abdominal obesity or upper body fat distribution is associated with increased risk of metabolic and cardiovascular disease. The purpose of the present study was to determine if a 24 week weight loss program with orlistat 60 mg in overweight subjects would produce a greater change in visceral adipose tissue (VAT) as measured by computed tomography (CT) scan, compared to placebo. The effects of orlistat 60 mg on changes in total fat mass (EchoMRI‐AH and BIA), ectopic fat (CT) and glycemic variables were assessed. One‐hundred thirty‐one subjects were randomized into a multicenter, double‐blind placebo controlled study in which 123 subjects received at least one post baseline efficacy measurement (intent‐to‐treat population). Both orlistat‐and placebo‐treated subjects significantly decreased their VAT at 24 weeks with a significantly greater loss of VAT by orlistat treated subjects (?15.7% vs. ?9.4%, P < 0.05). In addition, orlistat‐treated subjects had significantly greater weight loss (?5.93 kg vs. ?3.94 kg, P < 0.05), total fat mass loss (?4.65 kg vs. ?3.01 kg, P < 0.05) and trended to a greater loss of intermuscular adipose tissue and content of liver fat compared with placebo‐treated subjects. This is the first study to demonstrate that orlistat 60 mg significantly reduces VAT in addition to total body fat compared to placebo treated subjects after a 24 week weight loss program. These results suggest that orlistat 60 mg may be an effective weight loss tool to reduce metabolic risk factors associated with abdominal obesity.     

Substantial changes in epicardial fat thickness after weight loss in severely obese subjects

We sought to evaluate the effect of weight loss on echocardiographic epicardial fat thickness, as index of visceral adiposity, and whether epicardial fat change after the weight loss can be proportionally different from overall body weight changes and related to cardiac parameters changes in severely obese subjects. This was an interventional study in 20 severely obese subjects (12 women, 8 men, BMI 45+/-5 kg/m(2), 35+/-10 years) who underwent 6-month very low calorie diet weight loss program. Baseline and after 6-month weight loss anthropometrics, echocardiographic epicardial fat thickness, left ventricular mass (LVM), and diastolic function parameters were assessed. Subjects lost 20% of original body weight, BMI reduced by 19% of original BMI, waist circumference decreased by 23% of initial waist circumference. Epicardial fat thickness decreased from 12.3+/-1.8 to 8.3+/-1 mm P<0.001 after the 6-month very low calorie diet, as -32% of baseline epicardial fat thickness. LVM and diastolic function changes were better correlated with epicardial fat changes. We showed that significant weight loss can be associated with significant reduction in the epicardial fat thickness, marker of visceral adiposity in severely obese subjects. Epicardial fat decrease, therefore visceral fat decrease, can be proportionally higher than overall adiposity decrease. Epicardial fat changes are significantly associated with obesity-related cardiac morphological and functional changes during weight loss. Measurement of echocardiographic epicardial fat thickness may provide an additional tool in understanding the metabolic risk associated with variation in fat distribution.     

The Efficacy of Dietary Fat Vs. Total Energy Restriction for Weight Loss

Objective : Dietary fat restriction is currently being promoted as a weight loss strategy. However, previous investigations suggest that fat restriction alone may not be more beneficial than total energy restriction for the treatment of obesity. The purpose of this project was to assess whether an energy-restricted or fat-restricted diet was more effective at promoting weight loss, improving eating behaviors, and reducing barriers to dietary adherence. Research Methods and Procedures : Eighty individuals (15 men and 65 women) were randomized into the two treatment conditions. Subjects were 120% to 140% of ideal body weight and 25 years to 45 years old. Treatment consisted of 24 weeks of dietary fat (22 g/day to 26 g/day) or energy restriction (4,186 kJ/day to 5,023 kJ/day), including behavior modification and exercise. Body weight change, dietary intake, eating behaviors, and barriers to adherence were measured at baseline and after treatment. Results : Results show that subjects in the energy-restricted condition lost over twice as much weight as those in the fat-restricted group (11.5 kg vs. 5.2 kg). Additionally, subjects in the low-energy condition had greater improvements in eating behavior scores, enhanced feelings of wellness, a greater distaste for dietary fat, and no more pronounced feelings of deprivation than did those in the fat-restricted condition. Discussion : An energy-restricted diet produces greater short-term weight loss than dietary fat restriction without many of the negative consequences commonly attributed to reducing energy intake.     

Effects of yo-yo diet, caloric restriction, and olestra on tissue distribution of hexachlorobenzene

Chlorinated hydrocarbons are lipophilic, toxic, and persistent in the environment and animal tissues. They enter the body in food and are stored in adipose tissue. Loss of body fat through caloric restriction mobilizes stored lipophilic xenobiotics and results in distribution to other tissues. We have studied the reversibility of this process in mice that followed a regimen of body weight cycling. Weight gain was followed by weight loss, a second gain, and a second loss ("yo-yo diet regimen"). We measured the distribution of orally gavaged [14C]hexachlorobenzene, which is sparingly metabolized. We found that weight cycling has different effects in different organs. Continued weight loss resulted in a threefold increase of 14C amount and concentration in the brain. After weight regain, 14C in the brain decreased but then increased again after a second weight loss. Weight loss resulted in an increase in the concentration of 14C in adipose tissue without changing the total amount in that tissue. Weight loss and regain resulted in an increase of 14C in the liver, which reflected an increase of fat in the liver. The regimen of weight gain and loss was repeated in mice gavaged with [14C]hexachlorobenzene, with one group receiving the nonabsorbable fat olestra in the diet. Combined dietary olestra and caloric restriction caused a 30-fold increase in the rate of excretion of 14C relative to an ad libitum diet or a reduced caloric diet alone. Distribution of 14C into the brain resulting from the restricted diet was reduced by 50% by dietary olestra.     

Changes in body composition with weight loss: obese subjects randomized to surgical and medical programs

Objective: To assess changes in body composition with weight loss in obese subjects randomized to a laparoscopic adjustable gastric band surgical program or a medical program using a very‐low‐energy diet and orlistat. Research Methods and Procedures: Using body composition measurements by DXA, neutron activation for total body nitrogen, and whole body γ counting for total body potassium, we studied changes in fat mass, fat distribution, fat‐free mass, total bone mineral content, total body protein, and body cell mass at 6 (n = 61 paired) and 24 months (n = 53 paired) after randomization. Results: At 24 months, the surgical group had lost significantly more weight (surgical, 20.3 ± 6.5 kg; medical, 5.9 ± 8.0 kg). There was favorable fat‐free mass to fat mass loss ratios for both groups (surgical, 1:5.5; medical, 1:5.9). Changes in total body nitrogen or potassium were favorable in each group. A small reduction in mean bone mineral content occurred throughout the study but was not associated with extent of weight loss or treatment group. At 6 months, weight loss for both groups was similar (surgical, 14.1 ± 4.5 kg; medical, 13.3 ± 7.3 kg). The medical program subjects lost less fat‐free mass and skeletal muscle and had increased total body protein. The proportion of body fat to limb fat remained remarkably constant throughout the study. Discussion: Weight loss programs used in this study induced fat loss without significant deleterious effects on the components of fat‐free mass.     

Improvements in cardiovascular risk profile with large-volume liposuction: a pilot study

In this study, the authors investigated the physiologic effects of the altered body composition that results from surgical removal of large amounts of subcutaneous adipose tissue. Fourteen women with body mass indexes of greater than > 27 kg/m2 underwent measurements of fasting plasma insulin, triglycerides, cholesterol, body composition by dual-energy x-ray absorptiometry (DXA), resting energy expenditure, and blood pressure before and after undergoing large-volume ultrasound-assisted liposuction.There were no significant intraoperative complications. Body weight had decreased by 5.1 kg (p < 0.0001) by 6 weeks after liposuction, with an additional 1.3-kg weight loss (p < 0.05) observed between 6 weeks and 4 months after surgery, for a total weight loss of 6.5 kg (p < 0.00006). Body mass index decreased from (mean +/- SEM) 28.8 +/- 2.3 to 26.8 +/- 1.5 kg/m2 (p < 0.0001). This change in body weight was primarily the result of decreases in body fat mass: as assessed by DXA, lean body mass did not change (43.8 +/- 3.1 kg to 43.4 +/- 3.6 kg, p = 0.80), whereas DXA total body fat mass decreased from 35.7 +/- 6.3 to 30.1 +/- 6.5 kg (p < 0.0001). There were significant decreases in fasting plasma insulin levels (14.9 +/- 6.5 mIU/ml before liposuction versus 7.2 +/- 3.2 mIU/ml 4 months after liposuction, p < 0.007), and systolic blood pressure (132.1 +/- 7.2 versus 120.5 +/- 7.8 mmHg, p < 0.0002). Total cholesterol, high-density lipoprotein cholesterol, plasma triglycerides, and resting energy expenditure values were not significantly altered after liposuction.In conclusion, over a 4-month period, large-volume liposuction decreased weight, body fat mass, systolic blood pressure, and fasting insulin levels without detrimental effects on lean body mass, bone mass, resting energy expenditure, or lipid profiles. Should these improvements be maintained over time, liposuction may prove to be a valuable tool for reducing the comorbid conditions associated with obesity.     

A Randomized Double-Blind Crossover Study of the Antiobesity Effects of Etiocholanedione

Etiocholanedione (ED), a natural metabolite of dehy-droepiandrosterone, has antiobesity effects in animals when given orally and is nontoxic. We carried out a trial of oral ED in obese humans. In a 20-week randomized double-blind crossover study, 14 subjects lost significantly more weight and body fat during treatment with oral ED, 4 gm daily, than during placebo administration. Mean weight loss during ED administration was 2.8 ± 5.5 kilograms, which was equivalent to 0.53 k 0.91 kilograms per week per 100 kilograms of body fat; mean weight change during placebo administration was essentially zero: M.21 ± 4.2 kg, or 4.04 ± 0.74 kg/wk/100 kg body fat. The difference between the weight changes in the two periods was significant: for A kg, P<0.05; for Δ kg/wk/100 kg body fat, P<0.03. Densitometric measurement of body fat content showed that the mean weight loss coincided almost exactly with the mean decrease in fat content; thus, over the 10-week period of ED administration, the mean fat loss was about 5% of the initial body fat content. Three of the obese subjects had strikingly greater fat loss, about 18%, 19%, and 25% of the initial body fat content. There were no significant subjective or objective side effects of ED administration .     

Body fat,rank, and nutritional status in a captive group of Rhesus Macaques

Using weight and skinfold thickness to calculate relative body fat, the fat content of 21 captive female rhesus macaques was estimated. Although age and. pregnancy had no effect on fat, rank was significant, especially during winter, with high-rank females having the highest fat scores. Rank therefore has a significant effect on the health of captive animals and may also affect the health of individuals in feral groups.     

Recombinant human growth hormone, but not insulin-like growth factor-I, enhances central fat loss in postmenopausal women undergoing a diet and exercise program.

We examined the effect of recombinant human growth hormone (rhGH) and/or recombinant human insulin-like growth factor-I (rhIGF-l) on regional fat loss in postmenopausal women undergoing a weight loss regimen of diet plus exercise. Twenty-seven women aged 59-79 years, 20-40% above ideal body weight, completed a 12-week program consisting of resistance training 2 days/week and walking 3 days/week, while consuming a diet that was 500 kcal/day less than that required for weight maintenance. Participants were randomly assigned in a double-blind fashion to receive rhGH (0.025 mg/kg BW/day; n = 7), rhIGF-I (0.015 mg/kg BW/day; n = 7), rhGH + rhIGF-I (n = 6), or placebo (PL; n = 7). Regional and whole body fat mass were determined by dual X-ray absorptiometry. Body fat distribution was assessed by the ratios of trunk fat-to-limb fat (TrF/LimbF) and trunk fat-to-total fat (TrF/TotF). Limb and trunk fat decreased in all groups (p < 0.01). For both ratios of fat distribution, the rhGH treated group experienced an enhanced loss of truncal compared to peripheral fat (p < 0.01), with no significant change for those administered rhIGF-I or PL. There was no association between change in fat distribution and indices of cardiovascular disease risk as determined by serum lipidilipoprotein levels and maximal aerobic capacity. These results suggest that administration of rhGH facilitates a decrease in central compared to peripheral fat in older women undertaking a weight loss program that combines exercise and moderate caloric restriction, although no beneficial effects are conferred to lipid/lipoprotein profiles. Further, the effect of rhGH is not enhanced by combining rhGH with rhIGF-I administration. In addition, rhIGF-I does not augment the loss of trunk fat when administered alone.     

Fatness, menarche, and female fertility

It is hypothesized that a particular ratio of fat to lean mass is required for menarche and the maintenance of regular menstrual cycles. Females who lose 10-15% of normal weight for height, equivalent to a loss of 1/3 of body fat, become amenorrheic, presumably due to hypothalamic dysfunction. Adipose tissue may provide signals to the central nervous system and gonadotropin regulatory areas either directly, by estrogen production, or indirectly, by the effects of relative fatness on temperature control and metabolic rate, or by both means. Women with hypothalamic dysfunction experience changes in the secretion of gonadotropins, luteinizing hormone, follicle-stimulating hormone, and estrogen. Weight gain restores postmenarcheal secretion patterns. This approach suggests that the secular trend toward earlier age at menarche reflects earlier attainment of critical weight as a result of improved nutrition and child care. In many societies, subnutrition may explain the observed submaximum fertility. This suggests a need to integrate family planning programs with nutrition programs in many developing countries. It is important to note that the prediction of the minimum weight for height for onset and maintenance of ovulatory cycles is from total water as percentage of body weight. Although the percentage of fat in the body is inversely related to the percent of body water, only the latter is predictive. Successful prediction of the minimum weights for height is related to a lean mass/fat ratio represented by about 17% fat of body weight at menarche and 22% of body weight at the completion of growth at age 18 years.     

Induction of lipolysis in vitro and loss of body fat in vivo by zinc-alpha2-glycoprotein

Loss of adipose tissue in cancer cachexia has been associated with tumour production of a lipid-mobilizing factor (LMF) which has been shown to be homologous with the plasma protein zinc-alpha(2)-glycoprotein (ZAG). The aim of this study was to compare the ability of human ZAG with LMF to stimulate lipolysis in vitro and induce loss of body fat in vivo, and to determine the mechanisms involved. ZAG was purified from human plasma using a combination of Q Sepharose and Superdex 75 chromatography, and was shown to stimulate glycerol release from isolated murine epididymal adipocytes in a dose-dependent manner. The effect was enhanced by the cyclic AMP phosphodiesterase inhibitor Ro20-1724, and attenuated by freeze/thawing and the specific beta3-adrenoreceptor antagonist SR59230A. In vivo ZAG caused highly significant, time-dependent, decreases in body weight without a reduction in food and water intake. Body composition analysis showed that loss of body weight could be attributed entirely to the loss of body fat. Loss of adipose tissue may have been due to the lipolytic effect of ZAG coupled with an increase in energy expenditure, since there was a dose-dependent increase in expression of uncoupling protein-1 (UCP-1) in brown adipose tissue. These results suggest that ZAG may be effective in the treatment of obesity.     

Effect of Intermittent Cold Exposure on Brown Fat Activation,Obesity, and Energy Homeostasis in Mice

Homeotherms have specific mechanisms to maintain a constant core body temperature despite changes in thermal environment, food supply, and metabolic demand. Brown adipose tissue, the principal thermogenic organ, quickly and efficiently increases heat production by dissipating the mitochondrial proton motive force. It has been suggested that activation of brown fat, via either environmental (i.e. cold exposure) or pharmacologic means, could be used to increase metabolic rate and thus reduce body weight. Here we assess the effects of intermittent cold exposure (4°C for one to eight hours three times a week) on C57BL/6J mice fed a high fat diet. Cold exposure increased metabolic rate approximately two-fold during the challenge and activated brown fat. In response, food intake increased to compensate fully for the increased energy expenditure; thus, the mice showed no reduction in body weight or adiposity. Despite the unchanged adiposity, the cold-treated mice showed transient improvements in glucose homeostasis. Administration of the cannabinoid receptor-1 inverse agonist AM251 caused weight loss and improvements in glucose homeostasis, but showed no further improvements when combined with cold exposure. These data suggest that intermittent cold exposure causes transient, meaningful improvements in glucose homeostasis, but without synergy when combined with AM251. Since energy expenditure is significantly increased during cold exposure, a drug that dissociates food intake from metabolic demand during cold exposure may achieve weight loss and further metabolic improvements.     

Hyperleptinemia in obese adolescents deregulates neuropeptides during weight loss

Leptin has emerged over the past decade as a key hormone not only in energy balance regulation but also in neuroendocrine and inflammatory processes. The aim of the present study was to evaluate whether hyperleptinemia deregulates neuropeptides during weight loss. A total of 86 post-pubertal obese adolescents (with or without hyperleptinemia) participated in one year of interdisciplinary weight loss therapy (clinical, nutritional, psychological and exercise-related). Adipokine and neuropeptide concentrations were measured by ELISA, visceral fat was measured by ultrasound and body composition was measured by pletismography. The hyperleptinemic patients presented a lower alpha-MSH concentration and higher NPY/AgRP ratio while the adiponectin/leptin (A/L) ratio was lower compared with the non-hyperleptinemic group. After therapy, significant improvements in BM, BMI, body fat mass, visceral and subcutaneous fat, HOMA-IR, QUICKI, total cholesterol and triglycerides were observed in both groups. Indeed, we observed significant increases in adiponectin and A/L as well as reductions in leptin and NPY/AgRP ratio in the hyperleptinemic group. In the stepwise multiple linear regression analysis with leptin concentration as the dependent variable, α-MSH and body fat mass (%) were the independent predictors to explain leptin concentration. For the entire group, we found positive correlations between leptinemia and BMI and body fat mass (%) as well as a negative correlation with free fat mass (%) and alpha-MSH. Finally, we verified negative correlations between adiponectin/leptin ratio with total cholesterol and LDL-c, only in hyperleptinemic patients. In conclusion, the hyperleptinemia in obese adolescents deregulates neuropeptides during weight loss.     

Markers of inflammation and fat distribution following weight loss in African-American and white women

Changes in markers of inflammation (MOI) and fat distribution with weight loss between African-American (AA) and white (W) women have yet to be characterized. The purpose of this study was to examine potential ethnic differences in MOI and regional fat distribution with weight loss, and identify the associations between these markers and changes in regional fat distribution with weight loss among AA and W women. Subjects were 126 healthy, premenopausal women, BMI 27-30 kg/m(2). They were placed on a weight-loss intervention consisting of diet and/or exercise until a BMI <25 was achieved. Fat distribution was measured with computed tomography, and body composition with dual-energy X-ray absorptiometry. Serum concentrations of tumor necrosis factor-α (TNF-α), soluble TNF receptor-I (sTNFR-I), sTNFR-II, C-reactive protein (CRP), and interleukin-6 (IL-6) were assessed. All MOI and adiposity measures significantly decreased with weight loss. Significant ethnic differences with weight loss were observed for fat mass, body fat, intra-abdominal adipose tissue (IAAT), sTNFR-I, and sTNFR-II. Mixed-model analysis indicated that adjusting for change in IAAT explained ethnic differences in change in TNF-α and the decrease in TNF-α with weight loss, while total fat mass only explained the decrease in sTNFR-I and sTNFR-II with weight loss. In conclusion, all MOI decreased following weight loss among W, whereas only IL-6 and CRP decreased following weight loss in AA. The most distinct phenotypic difference observed was a greater impact of weight loss on TNF-α in W compared to AA, which was directly associated with IAAT in W.     

Interleukin‐15 Contributes to the Regulation of Murine Adipose Tissue and Human Adipocytes

An alarming global rise in the prevalence of obesity and its contribution to the development of chronic diseases is a serious health concern. Recently, obesity has been described as a chronic low‐grade inflammatory condition, influenced by both adipose tissue and immune cells suggesting proinflammatory cytokines may play a role in its etiology. Here we examined the effects of interleukin‐15 (IL‐15) on adipose tissue and its association with obesity. Over expression of IL‐15 (IL‐15tg) was associated with lean body condition whereas lack of IL‐15 (IL‐15^?/?) results in significant increase in weight gain without altering appetite. Interestingly, there were no differences in proinflammatory cytokines such as IL‐6 and tumor necrosis factor‐α (TNF‐α) in serum between the three strains of mice. In addition, there were significant numbers of natural killer (NK) cells in fat tissues from IL‐15tg and B6 compared to IL‐15^?/? mice. IL‐15 treatment results in significant weight loss in IL‐15^?/? knockout and diet‐induced obese mice independent of food intake. Fat pad cross‐sections show decreased pad size with over expression of IL‐15 is due to adipocyte shrinkage. IL‐15 induces weight loss without altering food consumption by affecting lipid deposition in adipocytes. Treatment of differentiated human adipocytes with recombinant human IL‐15 protein resulted in decreased lipid deposition. In addition, obese patients had significantly lower serum IL‐15 levels when compared to normal weight individuals. These results clearly suggest that IL‐15 may be involved in adipose tissue regulation and linked to obesity.     

Influence of the metabolic state during lactation on milk production in modern sows

Selection for prolificacy in sows has resulted in higher metabolic demands during lactation. In addition, modern sows have an increased genetic merit for leanness. Consequently, sow metabolism during lactation has changed, possibly affecting milk production and litter weight gain. The aim of this study was to investigate the effect of lactational feed intake on milk production and relations between mobilization of body tissues (adipose tissue or skeletal muscle) and milk production in modern sows with a different lactational feed intake. A total of 36 primiparous sows were used, which were either full-fed (6.5 kg/day) or restricted-fed (3.25 kg/day) during the last 2 weeks of a 24-day lactation. Restricted-fed sows had a lower milk fat percentage at weaning and a lower litter weight gain and estimated milk fat and protein production in the last week of lactation. Next, several relations between sow body condition (loss) and milk production variables were identified. Sow BW, loin muscle depth and backfat depth at parturition were positively related to milk fat production in the last week of lactation. In addition, milk fat production was related to the backfat depth loss while milk protein production was related to the loin muscle depth loss during lactation. Backfat depth and loin muscle depth at parturition were positively related to lactational backfat depth loss or muscle depth loss, respectively. Together, results suggest that sows which have more available resources during lactation, either from a higher amount of body tissues at parturition or from an increased feed intake during lactation, direct more energy toward milk production to support a higher litter weight gain. In addition, results show that the type of milk nutrients that sows produce (i.e. milk fat or milk protein) is highly related to the type of body tissues that are mobilized during lactation. Interestingly, relations between sow body condition and milk production were all independent of feed level during lactation. Sow management strategies to increase milk production and litter growth in modern sows may focus on improving sow body condition at the start of lactation or increasing feed intake during lactation.