Lipoprotein responses to weight loss and weight maintenance in high-risk obese subjects

OBJECTIVE: To examine changes in plasma lipids and lipoproteins after 51 months of reduced energy intake and sustained weight loss. METHODS: One-hundred patients were randomized to one of two dietary interventions for 3 months (weight loss period). Groups A and B received an energy-restricted diet plan of 5.2-6.3 MJ/day but group B was further instructed to replace two of three meals with a nutrient-fortified liquid meal replacement (MR). Upon completion of the weight loss period, all patients were given the same instructions regarding energy intake and were advised to use one MR daily. Body weight and 7 day food diaries were measured monthly or bimonthly and blood lipids at baseline, 3, 9 and 51 months. RESULTS: Of the original 100 patients 75 had completed 4 y. Of those 75, 73 had complete lipid records. Baseline body weights of Groups A and B were 90.7+/-14.0 and 91.6+/-9.8 kg, respectively. The percentage change in total cholesterol (%DeltaTC) decreased in a linear fashion with increasing weight loss, when all data was combined, but did not approach statistical significance (P< or =0.26, r=0.02). Further regression analysis found a significant negative linear relationship (P< or =0.0001, r=0.69) between initial total cholesterol (TC) concentrations and %DeltaTC. Hence, data from 27 of the 73 completers who exhibited an elevated serum total cholesterol (> or =6.2 mmol/l) were isolated and analyzed further. Baseline TC was 6.75+/-0.64, 5.85+/-0.63 at 9 months (P<0.05) and 5.76+/-0.52 mmol/l at 51 months (P<0.05). Similar values for VLDL-cholesterol were 1.33+/-0.80, 0.74+/-0.24 and 0.66+/-0.21 mmol/l by 51 months (P<0.05). Weight decreased by 5.2+/-5.1, 7.6+/-4.9 and 6.7+/-4.6% at 3, 9 and 51 months, respectively. CONCLUSION: Continuous energy restriction associated with a clinically meaningful weight loss significantly improved the lipid profile of high-risk patients. Similar weight and diet changes occurring in patients with normal plasma cholesterol were either increased or without affect.     

The effects of marked caloric restriction on lipoprotein lipase-activators in obese subjects

Lipoprotein lipase plays a major role in the clearance of triglyceride rich lipoproteins, chylomicrons and very low density lipoproteins, from the circulation and also contributes to production of high density lipoproteins. To be functional lipoprotein lipase requires an activator which is present in the serum. Generally, serum triglyceride correlates positively with serum lipoprotein lipase-activator levels. During caloric restriction both serum triglyceride and adipose tissue liproprotein activity decrease. Affect of caloric restriction on serum lipoprotein lipase activator levels in not known.In this study we have evaluated the effect of marked caloric restriction on the levels of serum triglyceride, total cholesterol high-density lipoprotein cholesterol and lipoprotein lipase-activator in morbidly obese subjects. Initially, twenty subjects were included in the study. Twenty subjects consumed a 320kcal protein supplemented modified fast diet for three weeks, fourteen subjects for seven weeks and eight subjects for eleven weeks. Weight loss was continuous throughout the study. Serum triglycerides decreased during the first three weeks (Baseline 156±9 mg/dl, third week 119±9 mg/dl, p<0.01), followed by a plateau between third and fifth weeks and a small increase, from the fifth through the eleventh weeks. At eleven weeks serum triglycerides were not significantly lower than at the onset of caloric restriction. Serum total-cholesterol changed similarly showing a rapid and significant decline during the first five weeks, a plateau between fifth and seventh weeks and a small increase between ninth to eleventh weeks. However, at eleven weeks, serum cholesterol was significantly lower (Baseline 216±13 mg/dl, eleventh week 140±5 mg/dl, p<0.01). Serum high-density lipoprotein cholesterol level decreased significantly only in female subjects (Baseline 53±2 mg/dl, third week 37±2 mg/dl, p<0.01). Serum lipoprotein lipase-activator level increased steadily reaching approximately 200% of initial levels at week eleven (p<0.01).Thus, it appears that severe caloric restriction in morbidly obese subjects was associated with a significant decrease in the serum total cholesterol, a significant decrease in HDL-cholesterol in women. These decreases seen in serum lipids were limited to the first five weeks despite a continuous weight loss throughout this study. Serum lipoprotein lipase-activator level increased steadily and changes in serum lipoprotein lipase activator levels did not follow the changes in serum triglyceride levels during the caloric restriction.     

Comparison of intermittent fasting versus caloric restriction in obese subjects: A two year follow-up

Objective

Caloric restriction (CR) is proven to be effective in increasing life span and it is well known that, nutritional habits, sleeping pattern and meal frequency have profound effects on human health. In Ramadan some Muslims fast during the day-light hours for a month, providing us a unique model of intermittent fasting (IF) in humans. In the present study, we have investigated the effects of IF versus CR on the same non-diabetic obese subjects who were followed for two years according to the growth hormone (GH)/Insulin like growth factor (IGF)-1 axis and insulin resistance.

Design

Single-arm Interventional Human Study.

Participants

23 female subjects (Body Mass Index (BMI) 29-39, aged between 28-42years).

Setting

Follow-up is designed as 12 months of CR, after which there was a month of IF and 11 months of CR again, to be totally 24 months. Subjects’ daily diets were aligned as low calorie diet during CR and during the IF period, the same subjects fasted for 15 hours in a day for a month and there was no daily calorie restriction. Nutritional pattern was changed as 1 meal in the evening and a late supper before sleeping and no eating and drinking during the day light hours in the IF model. Subjects made brisk walking twice a day during the whole follow-up including both CR and IF periods. BMI, Blood glucose, insulin, TSH, GH, HbA1c, IGF-1, Homa-IR and urinary acetoacetate levels were monitored once in three months and twice in the fasting month.

Measurements and Results

While subjects lost 1250 ± 372g monthly during the CR, in the IF period, weight loss was decreased to 473 ±146 g. BMI of all subjects decreased gradually and as the BMI decreased, glucose, HbA1c, insulin, Homa-IR and TSH levels were decreased. GH levels were at baseline at the beginning, increased in the first six months and stayed steady during the CR and IF period than began decreasing after the IF period, while IGF-I increased gradually during the CR period and beginning with the 7th day of IF period, it decreased and kept on decreasing till the end of the follow-up. Urinary acetoacetate levels were higher during the IF period suggesting a constant lipid catabolism.

Conclusion

Our results suggest that, CR affects metabolic parameters positively which will help especially pre-diabetic and insulin resistant patients without any pharmacological approach. In addition IF without calorie restriction can enhance health and cellular resistance to disease without losing weight and those effects may be attributed to different signalling pathways and circulating ketones during IF. Changes observed during IF are probably due to the changes in eating and sleeping pattern and thus changes in metabolic rhythm.

     

Sexual dimorphism in the response of adipose mass and cellularity to graded caloric restriction

OBJECTIVE: To investigate the effects of mild to moderate caloric restriction on parameters of body growth, fat mass, and adipose tissue cellularity in female and male Wistar rats. RESEARCH METHODS AND PROCEDURES: Three-month-old female and male Wistar rats were subjected to a chronic, mild to moderate caloric restriction paradigm (5%, 10%, or 20% reduction in caloric intake from ad libitum values) for 6 months. This was accomplished using a unique automated feeder system tailored to the food consumption levels of individual rats. Body weight and length, weight of lean organs, regional adipose mass, and adipose cellularity were measured before and after the diet restriction. RESULTS: Caloric restriction produced proportional decelerations in body weight increases in both genders, without significant changes in body length or lean organ mass. Marked and disproportional reductions in regional adipose tissue mass were produced at all levels of food restriction (even at 5% restriction). An unexpected finding was that in response to graded caloric restriction, female rats preserved adipose fat cell number at the expense of fat cell volume, whereas the converse was seen for male rats. DISCUSSION: These studies demonstrate a sexual dimorphism in the response to mild to moderate degrees of chronic caloric restriction. At low levels of caloric restriction, it is possible to affect regional adipose mass and cellularity while preserving lean organ mass.     

The association between measurement sites of visceral adipose tissue and cardiovascular risk factors after caloric restriction in obese Korean women

Quantities as well as distributions of adipose tissue (AT) are significantly related to cardiovascular disease (CVD) risk factors and can be altered with caloric restriction. This study investigated which cross-sectional slice location of AT is most strongly correlated with changes in CVD risk factors after caloric restriction in obese Korean women. Thirty-three obese pre-menopausal Korean women (32.4 ± 8.5 yrs, BMI 27.1 ± 2.3 kg/m²) participated in a 12 weeks caloric restriction program. Subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) were measured using computed tomography (CT) scans at the sites of L2-L3, L3-L4, and L4-L5. Fasting serum levels of glucose, insulin, triglyceride, total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), leptin and homeostasis model assessment-insulin resistance (HOMA-IR) were observed. Pearson''s partial correlation coefficients were used to assess the relationship between AT measurement sites and changes in CVD risk factors after calorie restriction. When calories were reduced by 350 kcal/day for 12 weeks, body weight (-2.7%), body fat mass (-8.2%), and waist circumference (-5.8%) all decreased (P < 0.05). In addition, following caloric restriction, serum levels of glucose (-4.6%), TC (-6.2%), LDL-C (-5.3%), leptin (-17.6%) and HOMA-IR (-18.2%) decreased significantly (P < 0.05) as well. Changes in VAT at the level of L3-L4 were significantly greater than those at other abdominal sites, and these changes were correlated with changes in TC (P < 0.05), LDL-C (P < 0.001), SBP (P < 0.001) and HOMA-IR (P < 0.01). These results show that VAT at L3-L4 had a stronger correlation with CVD risk factors than with other AT measurement sites after caloric restriction.     

Nutritional induction of adipose tissue lipoprotein lipase in obese subjects

Other workers have reported increased adipose tissue lipoprotein lipase after a weight loss in obese subjects and have suspected that this enzyme is a primary factor of pathophysiological significance. In order to determine whether this effect was the consequence of refeeding rather than weight loss, six obese females were included in a controlled study. Adipose tissue lipoprotein lipase was measured before weight loss, at the end of 30 days on a diet of 800 kcal/day (mean weight loss 8.7%), and four times during the 8 days after the initiation of refeeding a 1500 kcal/day mixed diet to insure weight stability. Adipose tissue lipoprotein lipase decreased by 77% by the end of the weight loss, and an average 2-fold increase (24.2 +/- 2.7 mean +/- sem versus/11.1 +/- 2.3 mU/10(6) cells, p less than 0.01) was shown as early as 2 days after refeeding. Peak values after refeeding did not surpass predieting values. Changes during restriction and peak postrefeeding values were both positively correlated to baseline values. It can be concluded that the previously shown increase in lipoprotein lipase during weight stability after a weight loss is likely to be a secondary effect of partial refeeding; the individual sensitivity of adipose tissue lipoprotein lipase to nutritional induction could be of critical importance.     

Alteration of amine oxidase activity in the adipose tissue of obese subjects

OBJECTIVE: To explore the activity of monoamine oxidases (MAOs) and semicarbazide-sensitive amine oxidases (SSAOs) in adipose tissue and blood of lean and moderately obese subjects and to study whether there is a link between these hydrogen peroxide-generating enzymes and blood markers of oxidative stress. RESEARCH METHODS AND PROCEDURES: Nine obese male subjects (BMI 32.6 +/- 0.4 kg/m(2)) and nine controls (BMI 23.4 +/- 0.5) of 24- to 40-year-old subjects were included in the study. MAO and SSAO activities were measured on microbiopsies of abdominal subcutaneous adipose tissue by quantifying (14)C-tyramine and (14)C-benzylamine oxidation. Levels of soluble SSAO, lipid peroxidation products, and antioxidant agents were measured in plasma, whereas cytoprotective enzymes were determined in blood lysates. RESULTS: The high MAO activity found in adipose tissue was diminished by one-half in obese subjects (maximum initial velocity of 1.2 vs. 2.3 nmol tyramine oxidized/mg protein/min). There was no change in SSAO activity, either under its adipose tissue-bound or plasma-soluble form. Plasma levels of lipid peroxidation products and antioxidant vitamins remained unmodified, as well as erythrocyte antioxidant enzymes, whereas circulating triglycerides, insulin, and leptin were increased. DISCUSSION: Although they already exhibited several signs of endocrino-metabolic disorders, the obese men did not exhibit the increase in blood markers of oxidative stress or the decrease in antioxidant defenses reported to occur in very obese or diabetic subjects. The reduced MAO and the unchanged SSAO activities found in obesity suggest that these hydrogen peroxide-generating enzymes expressed in adipocytes are probably not involved in the onset of the oxidative stress found in severe obesity and/or in its complications.     

Effect of a dietary supplement combination on weight management, adipose tissue, cholesterol and triglycerides in obese subjects

A combination dietary supplement containing vitamins, minerals, herbs, fibers and amino acids was studied to determine its safety and efficacy on weight/ fat loss, cholesterol and triglycerides in a double-blind, placebo-controlled trail. Total body weight, body fat %, waist and hip measurements, total cholesterol and triglycerides were evaluated before and after 6 weeks treatment with combination supplement or placebo. The study population consisted in 27 mildly to moderately obese, otherwise healthy, volunteers. After 6 weeks of treatment, the combination supplement had a statistically significant (p<0.001, mu=0.05) positive weight reducing effect (-8.59Lb vs. +2.14 Lb). This weight reduction was associated with a corresponding statistically significant (p<0.001, mu=0.05) decrease in body fat % in the treatment group (-2.88%) vs. the placebo (+0.86%). In addition, significant decreases in total cholesterol (-22.94 mg/dL) and triglycerides (-39.29 mg/dL) were obtained plus reductions in waist and hip measurements. These positive results lead us to conclude, that the combination supplement studied herein is a safe and effective way to assist in weight/fat reduction and decreases in total cholesterol and triglycerides in relatively short time (6 weeks).     

Isoproterenol decreases leptin expression in adipose tissue of obese humans.

OBJECTIVE: We investigated the effects of the non-selective beta-adrenergic agonist, isoproterenol (Iso), on leptin expression in human adipose tissue. RESEARCH METHODS AND PROCEDURES: Subcutaneous (SQ) and omental adipose (OM) tissue taken during surgery from 12 morbidly obese subjects (10 women and 2 men) were cultured for up to 24 hours with insulin (7 nM) and/or dexamethasone (25 nM), a synthetic glucocorticoid, in the presence or absence of isoproterenol (10 microM). Adipose tissue was also acutely incubated for 3 hours in media alone with or without isoproterenol. Leptin secretion and leptin mRNA abundance were measured. RESULTS: Iso acutely decreased leptin release by approximately 30% (vs. no hormone controls) in fragments of OM and SQ adipose tissue. In 24-hour culture, addition of Iso (in the presence of insulin) resulted in lower leptin accumulation in the medium (-20-30%) and leptin mRNA levels (-40-50%) from both tissue depots. Culture with insulin and dexamethasone increased leptin expression vs. insulin alone. Addition of Iso with insulin and dexamethasone decreased media leptin (-40-60%) and leptin mRNA levels were lower (-65%) in Iso-treated adipose tissue from both depots after 24 hours. Iso effects were not detectable after 5 hours of culture. DISCUSSION: We conclude that stimulation of beta-adrenergic receptors may modulate leptin expression in human adipose tissue by two mechanisms: an acute effect on leptin release and a longer-term antagonism of stimulatory effects of insulin and dexamethasone on leptin mRNA expression. These mechanisms may contribute to the decline in serum leptin that occurs during fasting.     

High expression of complement components in omental adipose tissue in obese men

OBJECTIVE: Accumulation of visceral fat is recognized as a predictor of obesity-related metabolic disturbances. Factors that are predominantly expressed in this depot could mediate the link between visceral obesity and associated diseases. RESEARCH METHODS AND PROCEDURES: Paired subcutaneous and omental adipose tissue biopsies were obtained from 10 obese men. Gene expression was analyzed by DNA microarrays in triplicate and by real-time polymerase chain reaction. Serum C3 and C4 were analyzed by radial immunodiffusion assays in 91 subjects representing a cross section of the general population. Body composition was measured by computerized tomography. RESULTS: Complement components C2, C3, C4, C7, and Factor B had higher expression in omental compared with subcutaneous adipose tissue ( approximately 2-, 4-, 17-, 10-, and 7-fold, respectively). In addition, adipsin, which belongs to the alternative pathway, and the classical pathway components C1QB, C1R, and C1S were expressed in both depots. Analysis of tissue distribution showed high expression of C2, C3, and C4 in omental adipose tissue, and only liver had higher expression of these genes. Serum C3 levels correlated with both visceral and subcutaneous adipose tissue in both men (r = 0.65 and p < 0.001 and r = 0.52 and p < 0.001, respectively) and women (r = 0.34 and p = 0.023 and r = 0.49 and p < 0.001, respectively), whereas C4 levels correlated with only visceral fat in men (r = 0.36, p = 0.015) and with both depots in women (visceral: r = 0.58, p < 0.001; and subcutaneous: r = 0.51, p < 0.001). DISCUSSION: Recent studies show that the metabolic syndrome is associated with chronically elevated levels of several immune markers, some of which may have metabolic effects. The high expression of complement genes in intra-abdominal adipose tissue might suggest that the complement system is involved in the development of visceral adiposity and/or contributes to the metabolic complications associated with increased visceral fat mass.     

Whole-body and adipose tissue glucose metabolism in response to short-term fasting in lean and obese women

BACKGROUND: Alterations in glucose metabolism during early fasting may be an important trigger of the hormonal and metabolic responses to fasting. OBJECTIVE: The purpose of this study was to determine whether glucose metabolism in response to brief starvation differs in lean and abdominally obese women. DESIGN: We evaluated whole-body glucose metabolism by use of stable-isotope tracer methods and glucose uptake in subcutaneous abdominal adipose tissue by use of arteriovenous balance in 7 lean [58 +/- 2 kg; body mass index (BMI; in kg/m(2)): 21 +/- 5] and 6 abdominally obese (96 +/- 2 kg; BMI: 36 +/- 1) women after 14 and 22 h of fasting. RESULTS: Between 14 and 22 h of fasting, whole-body glucose production and disposal declined in both groups (P < 0.05), but the reduction was 50% greater in lean than in obese women (P < 0.05). The decline in glucose uptake at 22 h of fasting was also lower in obese (0.11 +/- 0.04 micromol*100 g(-1) x min(-1)) than in lean (0.26 +/- 0.03 micromol x 100 g(-1) x min(-1)) women (P < 0.05). Decreases in plasma insulin and leptin concentrations between 14 and 22 h of fasting were also lower in obese than in lean women (insulin: 20 +/- 3% and 32 +/- 5%; leptin: 18 +/- 3% and 37 +/- 6%; both P < 0.05). CONCLUSIONS: The normal decline in glucose production and uptake that occurs during early fasting is blunted in women with abdominal obesity. These alterations in glucose metabolism are associated with a blunted decline in circulating concentrations of both insulin and leptin, which may explain some of the differences in the metabolic response to fasting observed between lean and abdominally obese persons.     

Topiramate: long-term maintenance of weight loss induced by a low-calorie diet in obese subjects

OBJECTIVE: To examine the safety and efficacy of topiramate (TPM) for maintaining weight following a low-calorie diet. RESEARCH METHODS AND PROCEDURES: Obese subjects (30 < or = BMI < 50 kg/m(2)) 18 to 75 years old received a low-calorie diet for 8 weeks. Those who lost > or =8% of their initial weight received TPM (96 or 192 mg/d) or placebo; all were on a lifestyle modification plan. Sixty weeks of medication were planned. Sponsor ended study early to develop a new controlled-release formulation with the potential to enhance tolerability and simplify dosing in this patient population. Efficacy was analyzed in subjects who completed 44 weeks of treatment before study termination. RESULTS: Of the 701 subjects enrolled, 80% lost > or =8% of their initial body weight and were randomized; 293 were analyzed for efficacy. Most withdrawals were due to premature termination of the study. Subjects receiving TPM lost 15.4% (96 mg/d) and 16.5% (192 mg/d) of their enrollment weight by week 44, compared with 8.9% in the placebo group (p < 0.001). Subjects on TPM continued to lose weight after the run-in, whereas those on placebo regained weight. Significantly more TPM subjects lost 5%, 10%, or 15% of their randomization weight than placebo. Most adverse events were related to the central nervous system. DISCUSSION: During a treatment period of 44 weeks, TPM was generally well tolerated, and subjects maintained weight loss initially achieved by a low-calorie diet-and produced additional clinically significant weight loss beyond that achieved by a low-calorie diet.     

Green tea supplementation upregulates uncoupling protein 3 expression in severe obese women adipose tissue but does not promote weight loss

Abstract

This study aims (i) to verify expression of the UCPs, PLIN1, PPARG2, and ADRB3 genes in the abdominal subcutaneous adipose tissue of obese women at baseline and after 8 weeks of supplementation with decaffeinated green tea extract, and (ii) to associate findings with clinical parameters. This is a longitudinal study during which 11 women with obesity grade III were submitted to supplementation with 450?mg of (–)-epigallocatechin gallate (EGCG) (intervention group); the control group consisted of 10 eutrophic women. Anthropometric parameters [weight, height, and body mass index (BMI)], resting metabolic rate (RMR, measured by indirect calorimetry), and gene expression (measured by real-time PCR, RT-qPCR) were determined before and after supplementation. After 8 weeks, clinical parameters and UCP1, PLIN1, PPARG2, and ADRB3 expression remained unaltered in the intervention group (p?>?.05). Genetic analysis also showed that the UCP3 gene was upregulated (p?=?.026), but its upregulation did not promote weight loss.     

Leptin receptor gene variation predicts weight change in subjects with impaired glucose tolerance

The leptin receptor (OB-R) gene is a promising candidate gene for type 2 diabetes, because leptin and its receptor play an important role in insulin secretion and the development of obesity. Therefore, we studied whether the pentanucleotide insertion polymorphism of the 3'-untranslated region (3'UTR) of the OB-R gene has an influence on the conversion from impaired glucose tolerance (IGT) to type 2 diabetes in the STOP-Noninsulin-Dependent Diabetes Mellitus trial. The STOP trial was a longitudinal, double-blind, placebo-controlled randomized trial that included 1429 subjects with IGT from high-risk populations. Using the restriction fragment length polymorphism method, we genotyped 770 subjects whose DNA was available for the insertion/deletion polymorphism of the 3'UTR of the OB-R gene. We did not find a relationship between the OB-R polymorphism and the conversion from IGT to type 2 diabetes (p = 0.747). However, the insertion allele was associated with a significant reduction in weight (p = 0.016), BMI (p = 0.009), and waist circumference (p = 0.006) in all subjects. Women carrying the I allele had a larger waist circumference change (p = 0.036), whereas men lost more weight and had a greater decrease in BMI. The pentanucleotide insertion/deletion polymorphism in the 3'UTR of the OB-R gene did not influence the conversion to type 2 diabetes in obese patients with IGT. However, this polymorphism was associated with a significant weight change, suggesting that it may potentially modulate the risk for type 2 diabetes.     

Low-carbohydrate diet versus caloric restriction: effects on weight loss, hormones, and colon tumor growth in obese mice

Our objective was to compare the effects of a low-carbohydrate diet to a high-carbohydrate/calorie-restricted diet on weight loss, hormones, and transplanted colon tumor growth. Eighty male C57BL/6 mice consumed a diet-induced obesity regimen (DIO) ad libitum for 7 weeks. From Weeks 8 to 14, the mice consumed a 1) DIO diet ad libitum (HF); 2) low-carbohydrate diet ad libitum (LC); 3) high-carbohydrate diet ad libitum (HC); or 4) HC calorie restricted diet (HC-CR). MC38 cells were injected at Week 15. At the time of injection, the HC-CR group displayed the lowest body weight (25.5 +/- 0.57 g), serum insulin-like growth factor I (IGF-I; 135 +/- 56.0 ng/ml), and leptin (1.0 +/- 0.3 ng/ml) levels. This group also exhibited the longest time to palpable tumor (20.1 +/- 0.9 days). Compared to the HF group, the HC group exhibited lower body weight (39.4 +/- 1.4 vs. 32.9 +/- 0.7 g, respectively), IGF-I (604 +/- 44.2 vs. 243.4 +/- 88.9 ng/ml, respectively), and leptin (15.6 +/- 2.2 vs. 7.0 +/- 0.7 ng/ml, respectively) levels but similar tumor growth. IGF-I levels were lower in the LC group (320.0 +/- 39.9 ng/ml) than the HF group, but tumor growth did not differ. These data suggest LC diets do not slow colon tumor growth in obese mice.     

Distinct effects of calorie restriction on adipose tissue cytokine and angiogenesis profiles in obese and lean mice

ABSTRACT: BACKGROUND: Obesity associates with low-grade inflammation and adipose tissue remodeling. Using sensitive high-throughput protein arrays we here investigated adipose tissue cytokine and angiogenesis-related protein profiles from obese and lean mice, and in particular, the influence of calorie restriction (CR). METHODS: Tissue samples from visceral fat were harvested from obese mice fed with a high-fat diet (60% of energy), lean controls receiving low-fat control diet as well as from obese and lean mice kept under CR (energy intake 70% of ad libitum intake) for 50 days. Protein profiles were analyzed using mouse cytokine and angiogenesis protein array kits. RESULTS: In obese and lean mice, CR was associated with 11.3% and 15.6% reductions in body weight, as well as with 4.0% and 4.6% reductions in body fat percentage, respectively. Obesity induced adipose tissue cytokine expressions, the most highly upregulated cytokines being IL-1ra, IL-2, IL-16, MCP-1, MIG, RANTES, C5a, sICAM-1 and TIMP-1. CR increased sICAM-1 and TIMP-1 expression both in obese and lean mice. Overall, CR showed distinct effects on cytokine expressions; in obese mice CR largely decreased but in lean mice increased adipose tissue cytokine expressions. Obesity was also associated with increased expressions of angiogenesis-related proteins, in particular, angiogenin, endoglin, endostatin, endothelin-1, IGFBP-3, leptin, MMP-3, PAI-1, TIMP-4, CXCL16, platelet factor 4, DPPIV and coagulation factor III. CR increased endoglin, endostatin and platelet factor 4 expressions, and decreased IGFBP-3, NOV, MMP-9, CXCL16 and osteopontin expressions both in obese and lean mice. Interestingly, in obese mice, CR decreased leptin and TIMP-4 expressions, whereas in lean mice their expressions were increased. CR decreased MMP-3 and PAI-1 only in obese mice, whereas CR decreased FGF acidic, FGF basic and coagulation factor III, and increased angiogenin and DPPIV expression only in lean mice. CONCLUSIONS: CR exerts distinct effects on adipocyte cytokine and angiogenesis profiles in obese and lean mice. Our study also underscores the importance of angiogenesis-related proteins and cytokines in adipose tissue remodeling and development of obesity.