2型糖尿病合并肥胖患者脂联素水平与胰岛素抵抗的相关性

目的 研究2型糖尿病合并肥胖患者脂联素水平和胰岛素抵抗之间的相关性,探讨脂联素在2型糖尿病合并肥胖患者发生胰岛素抵抗中的作用.方法 选择30例2型糖尿病合并肥胖患者、25例2型糖尿病患者及25例非糖尿病对照人员(其中13例为肥胖者),检测体质指数、腰/臀比值、空腹血糖、糖化血红蛋白、血清空腹胰岛素、血脂、脂联素水平,计算胰岛素抵抗指数和胰岛素敏感指数.分析血清脂联素与胰岛素抵抗的相关性.结果 (1)糖尿病肥胖组的检测体质指数、糖化血红蛋白、空腹血糖、胰岛素抵抗指数、血清空腹胰岛素、腰/臀比值均高于对照肥胖组,脂联素、胰岛素敏感指数低于对照肥胖组(P<0.05).(2)糖尿病非肥胖组甘油三酯、糖化血红蛋白、空腹血糖、胰岛素抵抗指数、血清空腹胰岛素均高于对照非肥胖组,胰岛素敏感指数、脂联素低于对照非肥胖组(P<0.05).(3)糖尿病肥胖组甘油三酯、胆固醇、体质指数、糖化血红蛋白、空腹血糖、胰岛素抵抗指数、血清空腹胰岛素、腰/臀比值均高于糖尿病非肥胖组,胰岛素敏感指数、脂联素低于糖尿病非肥胖组(P<0.05).结论 脂联素与2型糖尿病肥胖患者的胰岛素抵抗发生有关,脂联素降低易导致胰岛素抵抗,脂联素水平可作为2型糖尿病合并肥胖患者发生胰岛素抵抗的监测标准.     

非酒精性脂肪肝胰岛素抵抗及血清瘦素和脂联素水平的研究

[目的]研究非酒精性脂肪肝(NAFLD)患者胰岛素抵抗指数(IRI)、瘦素和脂联素水平的变化,探讨疾病发病中胰岛素抵抗(IR)、瘦素和脂联素的作用.[方法]测定体检和住院人群中NAFLD并肥胖(NAFLD)组、单纯性肥胖(肥胖)组和正常对照组空腹血糖、空腹血清胰岛素,采用稳态模型法计算IRI,同时检测瘦素和脂联素水平.[结果]NAFLD组空腹胰岛素水平和IRI显著高于肥胖组和对照组(P＜0.05);NAFLD组和肥胖组的瘦素水平显著高于对照组(P＜0.05);NAFLD组和肥胖组的脂联素水平显著低于对照组(P＜0.05);直线相关分析后,IRI与血清瘦素水平呈显著正相关(r=0.169 3,P＜0.01);而与血清脂联素水平呈显著负相关(r=-0.218 7,P＜0.01).[结论]IR可能是NAFLD发生、发展的基础,IR构成NAFLD患者基本特征之一,中央型肥胖是NAFLD的危险因素;NAFLD患者瘦素水平升高而脂联素水平降低,瘦素和脂联素通过不同机制参与了IR的发生、发展,进而影响NAFLD的发病.     

初发2型糖尿病患者血脂联素和瘦素与胰岛素抵抗的关系

目的 研究初发2型糖尿病患者血脂联素和瘦素水平的变化及其与胰岛素抵抗的关系.方法 选择46例初发2型糖尿病患者,及与其体脂含量相匹配的糖耐量正常者43名,计算体重指数(BMI)和腰臀围比(WHR),并空腹采血,测定血糖(FPG)、血脂、真胰岛素(FTI)、胰岛素原(FPI)、脂联素和瘦素浓度,分析血清脂联素和瘦素水平的变化及其与胰岛素抵抗的关系.用胰岛素抵抗指数(HOMA-IR)评估胰岛素抵抗程度.结果 2型糖尿病组与正常对照组比较,年龄、BMI无统计学意义(P>0.05),三酰甘油、FPG及FPI和HOMA-IR明显升高(P<0.05或P<0.01),舒张压、脂联素水平明显降低(P<0.05或P<0.01);相关分析显示,脂联素与FPG、FTI、HOMA-IR、BMI、WHR呈负相关(P<0.05或P<0.01);瘦素与BMI、FTI、HOMA-IR、FPG呈正相关(P<0.05或P<0.01),与WHR无关.人血清脂联素和瘦素间无相关性.结论 人血清脂联素和瘦素与胰岛素抵抗密切相关,体脂含量相同的初发2型糖尿病患者血脂联素水平低于正常人.     

脂联素/瘦素与胰岛素抵抗指数的相关性

目的研究健康人群、肥胖和2型糖尿病(T2DM)患者的血清脂联素/瘦素(APN/LEP)与胰岛素抵抗指数的关系。方法采用病例对照研究,2型糖尿病伴有肥胖组(DO)42例,T2DM不伴肥胖组(NDO)42例,单纯性肥胖组(OB)37例,正常对照组(NC)28名。检洲了4组研究对象血脂、血糖(FBG)、空腹胰岛素(Fins)、APN、LEP水平,用HOMA模型公式计算胰岛素抵抗指数(HOMA-IR)。结果正常对照组(NC)的脂联素/瘦素明显大于其它三组,统计学检验差异有显著性意义(P0.05),而其它三组间的脂联素/瘦素差异无显著性意义。糖尿病肥胖组(DO)的HOMA-IP明显高于其它三组,统计学检验差异有显著性意义(P0.05)。随着脂联素/瘦素的降低,胰岛素抵抗指数呈上升趋势。结论胰岛素抵抗指数与脂联素/瘦素间呈显著负相关,脂联素/瘦素有望成为反映胰岛素抵抗的新指标。     

青少年肥胖与胰岛素抵抗、血清脂联素水平及心理因素的关系

目的研究青少年肥胖与胰岛素抵抗、血清脂联素水平及心理因素的关系。方法中学生健康体检时选择体质量指数（BMI）在同年龄、同性别第95百分位数或以上者47例为肥胖组,对照组50例。检查血压、血糖、血脂、胰岛素和脂联素等指标,计算胰岛素抵抗指数,双能χ线吸收法检查体脂含量,采用症状自评量表评价心理状况。结果肥胖组血压、BMI、空腹胰岛素、血清TG、胰岛素抵抗指数、总体脂及躯干部体脂百分比高于对照组,而血清脂联素水平显著低于对照组。总体脂、躯干部体脂百分比和胰岛素抵抗指数是血清脂联素独立相关因素,为负性相关。肥胖组心理问题高于对照组,尤其在抑郁、焦虑和人际关系方面明显升高。结论青少年肥胖导致心理问题明显增加,血清脂联素与青少年肥胖呈负相关。     

高脂喂养对ApoE-/-小鼠脂肪细胞因子的影响

目的 探讨高脂诱导胰岛素抵抗(IR)对ApoE-/-小鼠内脂素(Visfatin)和脂联素的影响.方法 健康雄性ApoE-/-小鼠,随机分为普食组(NF)和高脂喂养组(HF),共喂养16 w.采用以3-H3葡萄糖为示踪剂的高胰岛素-正糖钳夹评价糖代谢变化.用实时荧光定量PCR测定肝和脂肪组织细胞因子Visfatin和脂联素mRNA表达水平,采用Western印迹法测定肝、脂肪组织及血浆Visfatin蛋白水平.结果 HF组小鼠空腹血糖、血浆胰岛素、胆固醇、游离脂肪酸、甘油三酯、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)水平明显升高(均P<0.01).胰岛素钳夹术中,HF组葡萄糖输注率(GIR)明显低于NF组,肝糖生成率(HGP)明显高于NF组(均P<0.01).HF组小鼠肝脏Visfatin和脂联素mRNA表达水平以及脂肪组织Visfatin mRNA表达水平明显低于NF组(P<0.01和P<0.05);HF组血浆、肝脏和脂肪组织Visfatin蛋白表达也显著降低均(均P<0.01).结论 高脂喂养的ApoE-/-小鼠具备明显的IR基本特征,可能与脂肪细胞因子的改变有关.     

脂联素与糖尿病及其临床问题

代谢综合征与肥胖及胰岛系抵抗有关.成人肥胖的特征是脂肪细胞体积增大,而脂肪组织分泌一些有生物活性的脂肪激素参与机体内能量平衡的调节.在转脂联素基因或脂联素基因剔除小鼠中功能分析中发现,脂联素是一个有胰岛素增敏作用的脂肪激素.事实上,肥胖对脂联素的降调节是肥胖导致胰岛素抵抗和糖尿病的一个机制.     

血清脂肪因子与代谢综合征的关系

121例代谢综合征(MS)患者和120名对照者入选本研究以探讨血清脂肪因子与MS的关系.对照组、非腹型肥胖MS组及腹型肥胖MS组的血清抵抗素和脂肪细胞型脂肪酸结合蛋白(A-FABP)依次增高,而脂联素水平依次降低(均P<0.05).MS组抵抗素与体重指数(BMI)、腰围、收缩压、空腹血糖和A-FABP呈正相关(P<0.05或P<0.01);脂联素与高密度脂蛋白胆固醇呈正相关,而与BMI、腰围、空腹胰岛素、甘油三酯、稳态模型评估的胰岛素抵抗指数(HOMA-IR)呈负相关.     

肝硬化患者血清脂联素与瘦素的相关性

目的测定肝硬化患者血清脂联素与瘦素的水平并探讨二者的相关性。方法测定73例肝硬化患者和30例健康对照的血清脂联素和瘦素及相关的临床生化参数,计算血清脂联素/瘦素比值。结果肝硬化患者血清脂联素、瘦素水平明显高于正常对照组(P<0.05);脂联素/瘦素比值>1;血清脂联素与瘦素水平呈正相关。血清脂联系、瘦素水平与胰岛素、胰岛素抵抗指数呈正相关,与胰岛素敏感指数呈负相关。结论肝硬化患者血清脂联素、瘦素水平和脂联素/瘦素比值明显升高,可能与肝硬化患者胰岛素抵抗有关。     

吡格列酮联合二甲双胍对2型糖尿病患者胰岛素抵抗及脂肪细胞因子水平的影响

目的观察吡格列酮联合二甲双胍治疗2型糖尿病(T2DM)的疗效,探讨治疗对患者胰岛素抵抗及脂肪细胞因子水平的影响。方法将我院收治的T2DM患者72例随机分为观察组和对照组,每组36例。对照组给予口服二甲双胍治疗,观察组给予二甲双胍联合盐酸吡格列酮治疗。观察两组患者治疗前后空腹血糖(FPG)、餐后2 h血糖(2 h PBG)、糖化血红蛋白(HbA1c)、空腹胰岛素(F-INS)和胰岛素抵抗指数(Homa IR)。并应用酶联免疫吸附法(ELISA)检验两组治疗前后血浆瘦素和脂联素水平。结果治疗后两组患者FPG、2 h PBG、HbA1c和Homa IR均显著降低(均P<0.05);治疗后研究组2 h PBG、HbA1c和Homa IR显著低于对照组(均P<0.05);治疗前两组瘦素和脂联素比较无统计学差异(均P>0.05),治疗结束后两组患者血清瘦素均显著降低,血清脂联素显著升高(均P<0.05),研究组血清瘦素显著低于对照组,血清脂联素显著高于对照组(P<0.05)。结论吡格列酮联合二甲双胍治疗可以有效调节T2DM患者瘦素和脂联素水平,进一步改善患者胰岛素抵抗。     

Inhibition of 11β-hydroxysteroid dehydrogenase type 1 reduces food intake and weight gain but maintains energy expenditure in diet-induced obese mice

Aims/hypothesis The 11β-hydroxysteroid dehydrogenase type-1 inhibitor BVT.2733 lowers blood glucose and insulin in mutant mouse models of obesity and diabetes. Its effects on energy balance and body composition, and their contribution to improved glucose homeostasis have received little attention.Materials and methods BVT.2733 (100 mg/kg, orally) was given twice daily to lean and diet-induced obese mice for 16 or 17 days. A group of obese mice was pair-fed to the amounts consumed by BVT.2733-treated mice.Results In both obese and lean mice, BVT.2733 reduced food intake and weight gain, but increased water intake. Pair-feeding caused almost as great a decrease in body weight as BVT.2733. Energy expenditure was 38±8% higher in the BVT.2733-treated obese mice than in the pair-fed mice. Terminal plasma corticosterone was raised, lean body weight reduced and percentage fat unchanged in the pair-fed mice (control, 47.8±2.6%; pair-fed, 47.1±1.9%), whereas BVT.2733 did not reduce lean mass, but did reduce percentage fat (40.9±2.0%). BVT.2733 but not pair-feeding reduced both the glucose tolerance AUC and the plasma insulin concentration 30 min after giving glucose.Conclusions/interpretation BVT.2733 reduced food intake but prevented a concomitant reduction in lean body mass and energy expenditure. The latter effects may have contributed to improved glucose tolerance.     

Adipose tissue-targeted 11β-hydroxysteroid dehydrogenase type 1 inhibitor protects against diet-induced obesity

Current pharmacological treatments for obesity and metabolic syndrome have various limitations. Recently, adipose tissue 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) has been proposed as a novel therapeutic target for the treatment of obesity and metabolic syndrome. Nevertheless, there is no adipose tissue-targeted 11β-HSD1 inhibitor available now. We sought to develop a new 11β-HSD1 pharmacological inhibitor that homes specifically to the white adipose tissue and aimed to investigate whether adipose tissue-targeted 11β-HSD1 inhibitor might decrease body weight gain and improve glucose tolerance in diet-induced obesity mice. BVT.2733, an 11β-HSD1 selective inhibitor was connected with a peptide CKGGRAKDC that homes to white fat vasculature. CKGGRAKDC-BVT.2733 (T-BVT) or an equimolar mixture of CKGGRAKDC and BVT.2733 (NT-BVT) was given to diet-induced obesity mice for two weeks through subcutaneous injection. T-BVT decreased body weight gain, improved glucose tolerance and decreased adipocyte size compared with vehicle treated mice. In adipose tissue T-BVT administration significantly increased adiponectin, vaspin mRNA levels; In liver T-BVT administration decreased the mRNA level of phosphoenolpyruvate carboxykinase (PEPCK), increased the mRNA levels of mitochondrial carnitine palmi-toyltransferase-I (mCPT-I) and peroxisome proliferator-activated receptorα(PPARα). No significant differences in adipocyte size and hepatic gene expression were observed after treatment with NT-BVT compared with vehicle treated mice, though NT-BVT also decreased body weight gain, improved glucose tolerance, and increased uncoupling protein-2 (UCP-2) mRNA levels in muscle. These results suggest that an adipose tissue-targeted pharmacological inhibitor of 11β-HSD1 may prove to be a new approach for the treatment of obesity and metabolic syndrome.     

Effects of pioglitazone and metformin on plasma adiponectin in newly detected type 2 diabetes mellitus

OBJECTIVE: This prospective study evaluates the effect of insulin sensitizers, pioglitazone (PGZ) and metformin (MET) on plasma adiponectin and leptin levels in subjects newly diagnosed with type 2 diabetes mellitus (T2DM). DESIGN: Double blind, randomized, active control, dose escalation study of 12 weeks treatment duration. PATIENTS: Thirty apparently healthy, treatment-naive T2DM patients diagnosed within the past 6 months. MEASUREMENTS: Plasma adiponectin and leptin levels were estimated by enzyme-linked immunosorbent assay (ELISA), and insulin resistance by the homeostasis model of assessment (HOMA-IR). RESULTS: Baseline plasma levels of adiponectin were lower in diabetic (n = 30) subjects than matched controls (n = 10, 6.6 +/- 1.1 vs 10.4 +/- 4.2 microg/ml, P = 0.021). The 12-week treatment with PGZ significantly increased adiponectin concentrations (6.6 +/- 1.1-17.9 +/- 7.4 microg/ml, P < 0.001) with no alteration in the MET treated group (6.8 +/- 1.5-6.7 +/- 2.8 microg/ml, P = 0.9). A significant decrease in plasma leptin levels was observed in the MET treated group (32.0 +/- 28.9-21.4 +/- 23.3 ng/ml, P = 0.024) but not in the PGZ treated group (23.9 +/- 24.1-22.4 +/- 25.4 ng/ml, P = 0.69). The alterations in plasma adiponectin and leptin levels were not associated with any change in body mass index (BMI). PGZ therapy improved insulin sensitivity to a greater degree (P = 0.007 and P = 0.001 for fasting plasma insulin (FPI) and HOMA-IR, respectively) than MET (P = 0.75 and P = 0.02 for FPI and HOMA-IR, respectively) but this improvement was not significantly different from that of MET at the end of 12 weeks (P = 0.146 and P = 0.09 for FPI and HOMA-IR, respectively). However, improvement in insulin sensitivity with PGZ was not commensurate with the increase in adiponectin. Better control of postbreakfast plasma glucose (PBPG) as well as decrease in serum triglycerides (TGs) were also seen with PGZ (PBPG, P < 0.001; TGs, P = 0.013). The rest of the parameters were comparable. Adverse reactions reported were minor and did not result in treatment discontinuation. CONCLUSIONS: Pioglitazone therapy appears to be better in achieving glycaemic control and increasing plasma adiponectin and insulin sensitivity in newly detected type 2 diabetics.     

Green coffee bean extract improves obesity by decreasing body fat in high-fat diet-induced obese mice

Objective:To evaluate possible lipid catabolism and body fat regulation effects of 3-caffeoylquinic acid in Green coffee bean extract(GCBE) in high-fat diet(HFD)-induced obese mice.Methods:Obesity was induced in mice using a HFD for four weeks.Then,mice were fed only HFD or HFD with GCBE at 50,100,and 200 mg/kg.Fatty acid synthesis mechanism regulation of body fat was investigated through real-time PCR and Western blot assay.Body fat reduction was measured through dual-energy X-ray absorptiometry.Results:In HFD-induced obese mice,GCBE treatment significantly decreased body weight gain,liver weight and white adipose tissue weights with regulation of adipose tissue lipolysis hormones,like adiponectin and leptin.GCBE treatment decreased mR NA expression levels of adipogenesis and adipocyte metabolism related genes in adipose tissues and the liver,and decreased the corresponding protein expression.Dual energy X-ray absorptiometry measurements were used to compare body fat between mice on high-fat and those treated with GCBE.GCBE treated mice had a lower fat mass compared to HFD alone fed mice and relative body weight and fat mass were markedly decreased.Conclusions:GCBE has a potential anti-obesity effect with lowering body fat accumulation by regulating adipogenesis and lipid metabolism-related genes and proteins in WAT and liver.     

Effects of dietary fibers on weight gain, carbohydrate metabolism, and gastric ghrelin gene expression in mice fed a high-fat diet

Diets that are high in dietary fiber are reported to have substantial health benefits. We sought to compare the metabolic effects of 3 types of dietary fibers -- sugarcane fiber (SCF), psyllium (PSY), and cellulose (CEL) -- on body weight, carbohydrate metabolism, and stomach ghrelin gene expression in a high-fat diet-fed mouse model. Thirty-six male mice (C57BL/6) were randomly divided into 4 groups that consumed high-fat diet alone (HFD) or high-fat diet containing 10% SCF, PSY, and CEL, respectively. After baseline measurements were assessed for body weight, plasma insulin, glucose, leptin, and glucagon-like peptide 1 (GLP-1), animals were treated for 12 weeks. Parameters were reevaluated at the end of study. Whereas there was no difference at the baseline, body weight gains in the PSY and SCF groups were significantly lower than in the CEL group at the end of study. No difference in body weight was observed between the PSY and SCF animals. Body composition analysis demonstrated that fat mass in the SCF group was considerably lower than in the CEL and HFD groups. In addition, fasting plasma glucose and insulin and areas under the curve of intraperitoneal glucose tolerance test were also significantly lower in the SCF and PSY groups than in the CEL and HFD groups. Moreover, fasting plasma concentrations of leptin were significantly lower and GLP-1 level was 2-fold higher in the SCF and PSY mice than in the HFD and CEL mice. Ghrelin messenger RNA levels of stomach in the SCF group were significantly lower than in the CEL and HFD groups as well. These results suggest differences in response to dietary fiber intake in this animal model because high-fat diets incorporating dietary fibers such as SCF and PSY appeared to attenuate weight gain, enhance insulin sensitivity, and modulate leptin and GLP-1 secretion and gastric ghrelin gene expression.     

Decreased plasma adiponectin levels in young obese males

Plasma adiponectin levels are reduced in middle-aged obesity and in patients with type 2 diabetes and coronary artery disease. The purpose of this study was to investigate the effects of early-aged obesity on plasma adiponectin level. Twenty-six male college students (19.2 +/- 1.1 years, obese group: n = 15, [body mass index > 25, percent body fat > 25%], non-obese group: n = 11) participated in the present study. We measured anthropometric parameters and plasma adiponectin and leptin level. Plasma adiponectin levels in the obese group were significantly lower than those in the non-obese group (obese: 4.7 +/- 2.0 micro g/ml, non-obese: 6.8 +/- 2.2 micro g/ml, p < 0.05). On the other hand, plasma leptin levels in the obese group were significantly higher than those in the non-obese group (obese: 8.4 +/- 3.2 ng/ml, non-obese: 2.6 +/- 2.1 ng/ml, p < 0.001). Plasma adiponectin levels were significantly correlated with body weight (r = -0.415, p < 0.05) and percent body fat (r = -0.412, p < 0.05). Stepwise multiple regression analysis revealed that percent body fat was a significant independent predictor of plasma adiponectin level (r = 0.406, p < 0.05). These results show that obesity is associated with reduced plasma adiponectin even in young subjects.     

Adipocytokine changes caused by low-carbohydrate compared to conventional diets in obesity

Modest weight loss causing a decrease in insulin resistance has been linked to favorable changes in the adipocyte cytokines leptin, adiponectin, and tumor necrosis factor-alpha (TNF-alpha), three emerging risk factors of cardiovascular disease. We previously observed a significant reduction in insulin resistance with weight loss in obese subjects on a low-carbohydrate diet. Based on these previous findings, we hypothesize that a low-carbohydrate diet would be more beneficial in changing leptin, TNF-alpha, and adiponectin than a conventional diet. A total of 75 severely obese (body mass index >/=35 kg/m(2)) subjects were randomized to instruction of 6 months of a low-carbohydrate diet or a conventional calorie-restricted diet. Serum levels of leptin, TNF-alpha, TNF-alpha-soluble receptor 1 (TNF-alpha SR1), and adiponectin were measured at baseline and after 6 months of dietary intervention. Subjects on low-carbohydrate diets experienced a greater decrease in leptin when compared to conventional dieters (p < 0.001). TNF-alpha increased significantly in nondiabetic subjects on conventional vs. low-carbohydrate diets (p = 0.003). Adiponectin and TNF-alpha SR1 change were not significantly different between diets. This is the first study to report the effects of dietary macronutrient alterations on serum adipocytokines in a randomized controlled trial. The greater reduction in insulin resistance and weight on a low-carbohydrate diet, in the short term, translates into greater improvement in leptin but with no significant improvements in TNF-alpha or adiponectin in patients with moderate to severe obesity after 6 months of dietary intervention.     

Plasma resistin, adiponectin and leptin levels in lean and obese subjects: correlations with insulin resistance

OBJECTIVE: Adipose tIssue regulates insulin sensitivity via the circulating adipocytokines, leptin, resistin and adiponectin. The objective of this study was to compare the levels of resistin, adiponectin and leptin in lean and obese subjects and determine the relationship between circulating adipocytokines and insulin resistance. METHODS: We examined plasma levels of resistin, adiponectin and leptin in 17 lean subjects with a mean body mass index (BMI) of approximately 23 and 34 non-diabetic obese individuals with a mean BMI approximately 33. Insulin resistance was assessed using the homeostasis model assessment ratio (HOMA-R) formula derived from fasting insulin and glucose levels. RESULTS: Resistin levels were not significantly different between the two groups but were significantly higher in women compared with men, 35.4+/-6.5 (s.e.) vs 15.4+/-2.9 microg/L, P<0.01. Resistin did not correlate with BMI but did significantly correlate with HOMA-R, P<0.01, and this correlation remained significant after adjustment for gender and BMI. Adiponectin levels were significantly lower in obese compared with lean subjects, P<0.005, and higher in women, P<0.001, but showed no significant correlation with HOMA-R. Leptin levels were significantly higher in obese subjects and women and correlated with HOMA-R and resistin. DISCUSSION: In this small group of patients we demonstrated that insulin resistance correlated most strongly with leptin levels. A significant correlation between resistin levels and insulin resistance was also observed. Although a similar trend was apparent for adiponectin, the correlation with insulin resistance did not achieve statistical significance.     

Decreased insulin sensitivity and increased oxidative damage in wasting adipose tissue depots of wild-type mice

Unintentional weight loss (wasting) in the elderly is a major health concern as it leads to increased mortality. Several studies have focused on muscle loss, but little is known about the mechanisms giving rise to loss of fat mass at old ages. To investigate potential mechanisms, white adipose tissue (WAT) characteristics and proteomic profiles were compared between adult (10-12-month-old) and aged (22-24-month-old) wild-type mice. Four individual WAT depots were analyzed to account for possible depot-specific differences. Proteomic profiles of WAT depots, along with body weights and compositions, plasma levels of insulin, leptin and adiponectin, insulin tolerance, adipocyte sizes, and products of oxidative damage in each WAT depot were determined. We found that lean mass remained constant while fat mass and insulin tolerance were decreased in old age, as were adipocyte sizes in the WAT depots. Proteomic results showed increased levels of enolase, pyruvate dehydrogenase E1β, NAD(+)-dependent isocitrate dehydrogenase α, and ATP synthase subunit β, and decreased levels of carbonic anhydrase 3 in WAT of aged mice. These data suggest increased aerobic glucose oxidation in wasting WAT, consistent with decreased insulin signaling. Also, Cu/Zn superoxide dismutase and two chaperones were increased in aged WAT depots, indicating higher stress resistance. In agreement, lipid peroxidation (HNE-His adducts) increased in old age, although protein oxidation (carbonyl groups) showed no increase. In conclusion, features of wasting WAT were similar in the four depots, including decreased adipocyte sizes and alterations in protein expression profiles that indicated decreased insulin sensitivity and increased lipid peroxidation.