The relationship of serum adipokines with malnutrition inflammation score in haemodialysis.

BACKGROUND: Protein-energy wasting is a prevalent disorder in haemodialysis. Zinc-α2-glycoprotein (ZAG) and adipose triglyceride lipase (ATGL) are novel adipokines with recognized lipolytic effects and proposed role in metabolic homoeostasis. This study was conducted to investigate the association of ZAG and ATGL concentrations with malnutrition-inflammation score (MIS) and metabolic profile of patients with haemodialysis. MATERIALS AND METHODS: Eighty-eight patients under regular haemodialysis were divided based on MIS to normal to mild wasting (NMW; n = 35) or moderate wasting (MW; n = 53) group. Anthropometric measurements along with fasting serum concentrations of ZAG, ATGL, free fatty acids (FFAs), albumin, transferrin, total iron-binding capacity (TIBC), hs-CRP, lipid profile and glucose metabolism were assessed. RESULTS: Adipose triglyceride lipase concentration was significantly higher in MW than NMW group (10·89 ± 5·7 vs. 8·02 ± 3·37 mIU/mL; P = 0·008). The ZAG and FFAs were not significantly different between two groups. ATGL was directly correlated with FFAs in all of the patients (r = 0·284, P = 0·007) and MW (r = 0·32, P = 0·021), and marginally in NMW (r = 0·31, P = 0·057) groups. ATGL and odds of having mild or moderate wasting were significantly correlated (OR = 1·21, P = 0·033). A positive association was observed between ATGL with TG (r = 0·31, P = 0·049) and also with transferrin and TIBC (r = 0·44, P = 0·001) only in MW group. An inverse relationship was observed between ATGL and HDL in all of the participants (r=-0·222, P = 0·04). No significant correlation was observed between ZAG and other parameters. CONCLUSIONS: The serum concentrations of ATGL, but not ZAG, were significantly higher in MW compared to NMW group. Each unit increase in ATGL concentrations was correlated with 21% increase in the odds of wasting severity. ATGL might play a role in wasting pathogenesis and metabolic profile in haemodialysis.

Recurrent lipoatrophic panniculitis of children.

BACKGROUND: Recurrent panniculitis in children with lipoatrophy has been loosely described and reported under different names, but has never been systematically evaluated by immunohistochemical stains. OBJECTIVE: To depict the profile of children with recurrent idiopathic panniculitis. METHODS: Study of clinical, histopathological and immunohistochemical features in five cases with recurrent idiopathic panniculitis. RESULTS: Five children with repeated attacks of painful subcutaneous nodules in association with fever, malaise and abdominal pain or arthralgia, with subsequent lipoatrophy were reviewed. In two patients, extensive involvement led to loss of the cutaneous fatty tissue. Laboratory abnormalities included increased acute phase reactants, leukocytosis with mild neutrophilia, microcytic anaemia and elevated liver enzymes. Histopathology showed lobar panniculitis without vasculitis and with a mixed infiltrate, composed of neutrophils, mononuclear cells, lymphocytes, macrophages and myeloid cells. Neutrophils and myeloid cells were more prominent in early lesions, whereas macrophages predominated in late stages, leading to lipophagia and lipoatrophy. Immunohistochemistry showed positive staining for myeloperoxidase around the necrotic adipocytes in early stages and CD68/PGM1 macrophages in late stages. Intense STAT1 staining was observed in the inflammatory infiltrate. All patients improved with methotrexate and corticosteroids. CONCLUSION: We present five cases of lobar panniculitis and lipoatrophy in childhood. The clinico-pathologic presentation shares features with other autoinflammatory diseases.

Association of Adipose Tissue Inflammation With Histologic Severity of Nonalcoholic Fatty Liver Disease.

BACKGROUND & AIMS: The prevalence of nonalcoholic fatty liver disease (NAFLD) has increased with the obesity pandemic. We analyzed the transcriptional profiles of subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT), and phenotypes and functional characteristics of adipocyte tissue macrophages (ATMs), in obese patients undergoing bariatric surgery. METHODS: We collected anthropometric data; plasma samples; and SAT, VAT, and liver tissues from 113 obese patients undergoing bariatric surgery at academic hospitals in Europe (Antwerp and Leuven) and South Africa. Based on clinical and histologic features, patients were assigned to the following groups: obese, NAFLD, nonalcoholic steatohepatitis (NASH), or NASH with fibrosis. Microarray analyses were performed to identify genes expressed differentially among groups. We measured levels of cytokines and chemokines in plasma samples and levels of RNAs in adipose tissues by quantitative reverse-transcription polymerase chain reaction. ATMs were isolated from patients and 13 lean individuals undergoing cholecystectomy (controls), analyzed by flow cytometry, and cultured; immunophenotypes and levels of cytokines and chemokines in supernatants were determined. RESULTS: We observed increased expression of genes that regulate inflammation in adipose tissues from patients with NAFLD and NASH; expression of these genes increased as disease progressed from NAFLD to NASH. We found 111 genes associated with inflammation that were expressed differentially between VAT and SAT. Serum levels of interleukin 8, chemokine (C-C motif) ligand 3, and tumor necrosis factor-α correlated with liver inflammation and NAFLD activity score. We developed 2 models that could be used to determine patients' liver histology based on gene expression in VAT and SAT. Flow cytometry showed increased proportions of CD11c+CD206+ and CCR2+ macrophages in VAT from patients with NASH, and supernatants of cultured macrophages had increased levels of cytokines and chemokines compared with controls. CONCLUSIONS: VAT and SAT from patients with NAFLD and NASH have an increased expression of genes that regulate inflammation, and ATM produce increased levels of inflammatory cytokines, compared with adipose tissues from controls. We identified an expression profile of 5 genes in SAT that accurately predict liver histology in these patients. Transcript profiling: accession numbers: GSE58979 and GSE59045.

Essential role of CD11a in CD8+ T-cell accumulation and activation in adipose tissue.

OBJECTIVE: T cells, particularly CD8(+) T cells, are major participants in obesity-linked adipose tissue (AT) inflammation. We examined the mechanisms of CD8(+) T-cell accumulation and activation in AT and the role of CD11a, a ß2 integrin. APPROACH AND RESULTS: CD8(+) T cells in AT of obese mice showed activated phenotypes with increased proliferation and interferon-γ expression. In vitro, CD8(+) T cells from mouse AT displayed increased interferon-γ expression and proliferation to stimulation with interleukin-12 and interleukin-18, which were increased in obese AT. CD11a was upregulated in CD8(+) T cells in obese mice. Ablation of CD11a in obese mice dramatically reduced T-cell accumulation, activation, and proliferation in AT. Adoptive transfer showed that CD8(+) T cells from wild-type mice, but not from CD11a-deficient mice, infiltrated into AT of recipient obese wild-type mice. CD11a deficiency also reduced tumor necrosis factor-α-producing and interleukin-12-producing macrophages in AT and improved insulin resistance. CONCLUSIONS: Combined action of cytokines in obese AT induces proliferative response of CD8(+) T cells locally, which, along with increased infiltration, contributes to CD8(+) T-cell accumulation and activation in AT. CD11a plays a crucial role in AT inflammation by participating in T-cell infiltration and activation.

Obesity is associated with acute inflammation in a sample of adolescents.

BACKGROUND: Obesity is associated with a mild chronic inflammatory response, which has been suggested to be pivotal in the development of cardiometabolic alterations of obesity. However, little is known about the involvement of acute inflammation. OBJECTIVE: To evaluate whether circulating neutrophils, markers of acute inflammation, are associated (quantitatively and qualitatively) with adolescent obesity and whether leptin modulates these associations. SUBJECTS AND METHODS: We assessed 528 adolescents (16.8 yr old, 47% females), without chronic/acute illness. We measured anthropometry and dual energy X-ray absorptiometry and calculated fat mass percentage (FM%). Fasting serum glucose, high-density lipoprotein (HDL)-cholesterol, and triglycerides were used with blood pressure and waist circumference to compute a metabolic z-score. Leukocyte and neutrophil counts were obtained, together with levels of serum leptin. In a subsample of 23 males, flow cytometry was used to assess degranulation (CD66b expression) of neutrophils. RESULTS: Female sex and obesity were positively related to mean neutrophil counts (p < 0.05). When accounting for sex and weight status, leptin was associated with neutrophil counts (p < 0.05), partially explaining the association between obesity and neutrophil counts. Neutrophil counts were related to metabolic risk z-scores, controlling for fat mass. Participants with elevated FM% showed more neutrophil degranulation than controls (p < 0.05). CONCLUSIONS: Participants with increased adiposity had higher circulating neutrophil counts, suggesting acute inflammation. Furthermore, the neutrophils showed more degranulation, indicating inflammation. Obesity-induced alteration of the adipose secretory pattern (i.e., changes in leptin levels) could be involved in acute inflammation.

Detection of anti-neutrophil cytoplasmic antibodies in dogs with immune-mediated inflammatory diseases.

Anti-neutrophil cytoplasmic antibody (ANCA) is a type of autoantibody against neutrophil cytoplasm. In veterinary medicine, few studies have reported the detection of ANCA in dogs, and most of these studies were performed in dogs with inflammatory bowel disease (IBD). The aim of this study was to evaluate whether ANCA is detected in dogs with immune-mediated inflammatory diseases (IMIDs) other than IBD. Serum samples were collected before treatment initiation from 40 client-owned dogs with various diseases and 22 healthy beagle dogs; the dogs were classified into two groups: IMID group (n = 16) and control group (n = 46). ANCA was detected using the indirect fluorescent antibody test. Of the 16 dogs in the IMID group, 13 (81.3%) tested positive for ANCA. In contrast, of the 46 dogs in the control group, 13 (28.03%) tested positive for ANCA. Moreover, a significant association between ANCA positivity and IMIDs was identified in the IMID group than in the control group (P = 0.0003). In the control group, however, dogs with bacterial infection showed a relatively high rate of ANCA positivity. Therefore, ANCA positivity was observed in dogs with both IMIDs and bacterial infection. This suggested that ANCA positivity is associated with diseases accompanied by neutrophil activation and infiltration.

Lavatera critica controls systemic insulin resistance by ameliorating adipose tissue inflammation and oxidative stress using bioactive compounds identified by GC-MS.

BACKGROUND: Lavatera critica, a leafy green herb, is reported to have many pharmacological activities; but, the improvement of insulin sensitivity against the high gram-fat diet (HGFD)-caused insulin resistance (IR) has not yet been studied. OBJECTIVE: This study evaluated the role of Lavatera critica leaf extract (LCE) in systemic insulin resistance through the alleviation of adipose tissue inflammation and oxidative damage in HGFD fed mice. METHODS: The mice were fed with HGFD for 10 weeks and the diet was supplemented with LCE each day for the next five weeks. Body weight, food intake, leptin, blood glucose, insulin, insulin resistance, and pro- and anti-inflammatory genes expression were assessed on day 106. RESULTS: The HGFD control mice displayed markedly elevated adipose tissue inflammation, oxidative stress, insulin inactivity, and hyperglycemia. Administration of LCE in the HGFD mice, especially a dose of 100 mg/kg, lowered the body weight, food intake, plasma leptin, plasma glucose, plasma insulin, insulin resistance, and increased the food efficacy ratio when compared with the HGFD control mice. The oral glucose tolerance test (OGTT) revealed that LCE prevented further increase in the circulating levels after the glucose load. LCE-treated mice demonstrated a marked suppression of pro-inflammatory cytokines mRNA expression. On the other hand, the mice showed a higher anti-inflammatory genes mRNA expression in the adipose tissue. In addition, LCE treatment improved the oxidative damage as evidenced by the reduced levels of lipid hydroperoxides and thiobarbituric acid reactive substances coupled with the increased antioxidants (superoxide dismutase, total glutathione, glutathione/glutathione disulfide ratio and glutathione peroxidase) in the adipose tissue, plasma and erythrocytes. Gas chromatography-mass spectrometry analysis of the bioactive compounds revealed the presence of 9, 12, 15-octadecatrienoic acid, vitamin E, phytol, hexadecanoic acid, benzenepropanoic acid, and stigmasterol. CONCLUSIONS: These findings prove that LCE improves the insulin-sensitizing activity in the mouse model of HGFD-caused IR, probably due to the amelioration of adipose tissue inflammation and oxidative damage. Hence, the LCE could serve as a useful anti-diabetic agent.

Fitness, adiposopathy, and adiposity are independent predictors of insulin sensitivity in middle-aged men without diabetes.

Adiposopathy, or sick fat, refers to adipose tissue dysfunction that can lead to several complications such as dyslipidemia, insulin resistance, and hyperglycemia. The relative contribution of adiposopathy in predicting insulin resistance remains unclear. We investigated the relationship between adiposopathy, as assessed as a low plasma adiponectin/leptin ratio, with anthropometry, body composition (hydrostatic weighing), insulin sensitivity (hyperinsulinemic-euglycemic clamp), inflammation, and fitness level (ergocycle VO2max, mL/kgFFM/min) in 53 men (aged 34-53 years) from four groups: sedentary controls without obesity (body mass index [BMI] <25 kg/m(2)), sedentary with obesity (BMI > 30 kg/m(2)), sedentary with obesity and glucose intolerance, and endurance trained active without obesity. The adiponectin/leptin ratio was the highest in trained men (4.75 ± 0.82) and the lowest in glucose intolerant subjects with obesity (0.27 ± 0.06; ANOVA p < 0.0001) indicating increased adiposopathy in those with obesity. The ratio was negatively associated with adiposity (e.g., waist circumference, r = -0.59, p < 0.01) and positively associated with VO2max (r = 0.67, p < 0.01) and insulin sensitivity (M/I, r = 0.73, p < 0.01). Multiple regression analysis revealed fitness as the strongest independent predictor of insulin sensitivity (partial R (2) = 0.61). While adiposopathy was also an independent and significant contributor (partial R (2) = 0.10), waist circumference added little power to the model (partial R (2) = 0.024). All three variables remained significant independent predictors when trained subjects were excluded from the model. Plasma lipids were not retained in the model. We conclude that low fitness, adiposopathy, as well as adiposity (and in particular abdominal obesity) are independent contributors to insulin resistance in men without diabetes.

Predictive Blood Chemistry Parameters for Pansteatitis-Affected Mozambique Tilapia (Oreochromis mossambicus).

One of the largest river systems in South Africa, the Olifants River, has experienced significant changes in water quality due to anthropogenic activities. Since 2005, there have been various "outbreaks" of the inflammatory disease pansteatitis in several vertebrate species. Large-scale pansteatitis-related mortality events have decimated the crocodile population at Lake Loskop and decreased the population at Kruger National Park. Most pansteatitis-related diagnoses within the region are conducted post-mortem by either gross pathology or histology. The application of a non-lethal approach to assess the prevalence and pervasiveness of pansteatitis in the Olifants River region would be of great importance for the development of a management plan for this disease. In this study, several plasma-based biomarkers accurately classified pansteatitis in Mozambique tilapia (Oreochromis mossambicus) collected from Lake Loskop using a commercially available benchtop blood chemistry analyzer combined with data interpretation via artificial neural network analysis. According to the model, four blood chemistry parameters (calcium, sodium, total protein and albumin), in combination with total length, diagnose pansteatitis to a predictive accuracy of 92 percent. In addition, several morphometric traits (total length, age, weight) were also associated with pansteatitis. On-going research will focus on further evaluating the use of blood chemistry to classify pansteatitis across different species, trophic levels, and within different sites along the Olifants River.

Altered Methylation Profile of Lymphocytes Is Concordant with Perturbation of Lipids Metabolism and Inflammatory Response in Obesity.

Obesity is associated with immunological perturbations that contribute to insulin resistance. Epigenetic mechanisms can control immune functions and have been linked to metabolic complications, although their contribution to insulin resistance still remains unclear. In this study, we investigated the link between metabolic dysfunction and immune alterations with the epigenetic signature in leukocytes in a porcine model of obesity. Global DNA methylation of circulating leukocytes, adipose tissue leukocyte trafficking, and macrophage polarisation were established by flow cytometry. Adipose tissue inflammation and metabolic function were further characterised by quantification of metabolites and expression levels of genes associated with obesity and inflammation. Here we show that obese pigs showed bigger visceral fat pads, higher levels of circulating LDL cholesterol, and impaired glucose tolerance. These changes coincided with impaired metabolism, sustained macrophages infiltration, and increased inflammation in the adipose tissue. Those immune alterations were linked to global DNA hypermethylation in both B-cells and T-cells. Our results provide novel insight into the possible contribution of immune cell epigenetics into the immunological disturbances observed in obesity. The dramatic changes in the transcriptomic and epigenetic signature of circulating lymphocytes reinforce the concept that epigenetic processes participate in the increased immune cell activation and impaired metabolic functions in obesity.

Unusual Acute Sequelae of α1-Antitrypsin Deficiency: A Myriad of Symptoms With One Common Cure.

Panniculitis associated with α1-antitrypsin deficiency (AATD) is well documented but rare. We report the first case, to our knowledge, of successful induction of clinical remission of AATD-related panniculitis following a single 120-mg/kg dose administration of plasma-purified α1-antitrypsin (AAT). A 23-year-old man with known PiZZ AATD presented to the hospital with a diffusely swollen and tender right upper limb. This was associated with subcutaneous induration, and a discrepancy of 5 cm in upper limb circumference at the mid arm was noted. There was no convincing precipitant for cellulitis or an infectious cause, and inflammatory markers were raised, with a C-reactive protein (CRP) level of 93.9 mg/L and erythrocyte sedimentation rate (ESR) of 71 mm/h. Doppler ultrasonography ruled out DVT. No antimicrobials or antiinflammatory medications were administered during or prior to admission. Biopsy specimens of the right upper limb revealed extensive panniculitis with neutrophils, foamy macrophages, and fat necrosis. A diagnosis of AATD-associated panniculitis was made. Following this, a single IV dose of 120 mg/kg of plasma-purified AAT was administered. By day 7 post AAT infusion, CRP level had normalized to 4.6 mg/L and ESR had dropped to 22 mm/h. Limb circumference discrepancy on day 7 was 1 cm. There was no tenderness to palpation or induration, and a clinical remission of panniculitis was observed. We report the first case, to our knowledge, of clinical remission following a single treatment with IV AAT at a dose of 120 mg/kg. This opens avenues to more timely and effective treatment of the more severe presentations of AAT-associated panniculitis.

Gastric bypass in morbid obese patients is associated with reduction in adipose tissue inflammation via N-oleoylethanolamide (OEA)-mediated pathways.

Paradoxically, morbid obesity was suggested to protect from cardiovascular co-morbidities as compared to overweight/obese patients. We hypothesise that this paradox could be inferred to modulation of the "endocannabinoid" system on systemic and subcutaneous adipose tissue (SAT) inflammation. We designed a translational project including clinical and in vitro studies at Geneva University Hospital. Morbid obese subjects (n=11) were submitted to gastric bypass surgery (GBS) and followed up for one year (post-GBS). Insulin resistance and circulating and SAT levels of endocannabinoids, adipocytokines and CC chemokines were assessed pre- and post-GBS and compared to a control group of normal and overweight subjects (CTL) (n=20). In vitro cultures with 3T3-L1 adipocytes were used to validate findings from clinical results. Morbid obese subjects had baseline lower insulin sensitivity and higher hs-CRP, leptin, CCL5 and anandamide (AEA) levels as compared to CTL. GBS induced a massive weight and fat mass loss, improved insulin sensitivity and lipid profile, decreased C-reactive protein, leptin, and CCL2 levels. In SAT, increased expression of resistin, CCL2, CCL5 and tumour necrosis factor and reduced MGLL were shown in morbid obese patients pre-GBS when compared to CTL. GBS increased all endocannabinoids and reduced adipocytokines and CC chemokines. In morbid obese SAT, inverse correlations independent of body mass index were shown between palmitoylethanolamide (PEA) and N-oleoylethanolamide (OEA) levels and inflammatory molecules. In vitro, OEA inhibited CCL2 secretion from adipocytes via ERK1/2 activation. In conclusion, GBS was associated with relevant clinical, metabolic and inflammatory improvements, increasing endocannabinoid levels in SAT. OEA directly reduced CCL2 secretion via ERK1/2 activation in adipocytes.

Alpha-1-antitrypsin associated panniculitis: the MS variant.

Over 90 mutant alleles of the alpha-1-antitrypsin (AAT) gene are recognized and classified by mobility on an acid starch gel. The four major categories include: F=fast, M=medium, S=slow, Z=very slow. Among 41 reported cases of AAT panniculitis, most have the ZZ phenotype with AAT levels below normal. We report two cases of AAT panniculitis with MS phenotype and normal AAT levels. In addition, we review the pathophysiology, epidemiology, and extracutaneous manifestations of AAT disease and propose a diagnostic algorithm for ulcerative panniculitis. A 42-year-old man presented with a solitary plaque on the left thigh exacerbated by trauma or excessive activity. The lesion frequently suppurated with a yellowish oily material. Twenty years before, he had fractured his left femur which was repaired with a metal plate. X-rays, histology with special stains for organisms, and cultures were negative. AAT phenotype was MS and AAT value was normal. A 43-year-old woman presented with multiple plaques on the proximal extremities which suppurated with exercise or trauma. AAT phenotype was MS and AAT level was normal. Histologic exam for both patients showed a dense neutrophilic infiltrate with septal and lobular panniculitis and areas of necrobiosis in the lower reticular dermis.

Additional tests of interest to the dermatologist.

The carcinoid syndrome and its clinical manifestations have been discussed. The standard laboratory test for making that diagnosis is urinary 5-HIAA levels but newer, more sensitive tests may also be available.

Cytophagic histiocytic panniculitis with atypical lymphocytes in peripheral blood.

A 26-year-old female patient developed high fever, hepatosplenomegaly and subcutaneous nodules. Atypical lymphocytes were present in the peripheral blood. Skin biopsy revealed lobular panniculitis. Bone marrow examination showed prominent phagocytosis by benign histiocytes. The diagnosis of cytophagic histiocytic panniculitis was made, and the disease has been well controlled with oral prednisolone. This is the first report of cytophagic histiocytic panniculitis with atypical lymphocytes in the peripheral blood, which are frequently seen in virus-associated hemophagocytic syndrome. This observation suggests that underlying viral infection may be one factor in the development of cytophagic histiocytic panniculitis.

Serum alpha 1-antitrypsin concentration in dogs with panniculitis.

OBJECTIVE: To measure serum alpha 1-antitrypsin (alpha 1AT) concentration in dogs with histologically confirmed panniculitis to determine whether serum deficiency could cause or exacerbate panniculitis in dogs. DESIGN: Cross-sectional, descriptive study. ANIMALS: 9 dogs (5 with multiple lesions and 4 with solitary lesions). PROCEDURE: Serum samples were obtained by means of cephalic or jugular venipuncture and frozen at -20 C until assayed. Serum alpha 1AT concentration was measured by means of radial gel immunodiffusion. RESULTS: In all dogs, serum alpha 1AT concentration was within the previously established reference range. CLINICAL IMPLICATIONS: In the small number of-dogs studied, panniculitis was not associated with serum alpha 1AT deficiency.

Adipose inflammation in obesity: relationship with circulating levels of inflammatory markers and association with surgery-induced weight loss.

CONTEXT: The inflammatory state of the adipose tissue is believed to contribute to systemic low-grade inflammation in obesity. OBJECTIVE: This study assessed the relationship between adipose and circulating inflammatory markers as well as the influence of adipose inflammation on bariatric surgery-induced weight reduction. DESIGN: This was a cross-sectional and longitudinal study (up to 14 mo). SETTING: The study was conducted in the digestive/bariatric surgery department of the Tivoli and Jean Villar clinics, Bordeaux, France. PATIENTS: Thirty-seven obese patients [body mass index (BMI)>35-40 kg/m2)] seeking bariatric surgery were included. Twenty-eight of them were successively followed up at 1-3 months after surgery and 25 between 6 and 14 months after surgery. MAIN OUTCOME MEASURES: Fasting serum samples were collected before surgery to assess concentrations of inflammatory markers. Samples of visceral adipose tissue were extracted during surgery and gene expression of cytokines and immune cell markers were evaluated using quantitative RT-PCR. Pre- and postsurgery weight and BMI were collected. RESULTS: Gene expression of several cytokines were strongly intercorrelated in the visceral adipose tissue. Adipose expression of macrophage and T cell markers were related to adipose expression of TNF-α and IL-1 receptor antagonist (P<.01) and to systemic levels of TNF-α (P<.01) and IL-6 (P<.05). A higher inflammatory state of the adipose tissue predicted a lower BMI reduction after surgery (P<.05), notably at early stages after surgery. CONCLUSIONS: These findings support the involvement of macrophages and T cells in adipose inflammation and provide new information regarding the role of the visceral adipose tissue in the inflammatory state of obesity and its impact on obesity treatment outcomes, such as surgery-induced weight loss.

Weight cycling enhances adipose tissue inflammatory responses in male mice.

BACKGROUND: Obesity is associated with low-grade chronic inflammation attributed to dysregulated production, release of cytokines and adipokines and to dysregulated glucose-insulin homeostasis and dyslipidemia. Nutritional interventions such as dieting are often accompanied by repeated bouts of weight loss and regain, a phenomenon known as weight cycling (WC). METHODS: In this work we studied the effects of WC on the feed efficiency, blood lipids, carbohydrate metabolism, adiposity and inflammatory markers in C57BL/6 male mice that WC two or three consecutive times by alternation of a high-fat (HF) diet with standard chow (SC). RESULTS: The body mass (BM) grew up in each cycle of HF feeding, and decreased after each cycle of SC feeding. The alterations observed in the animals feeding HF diet in the oral glucose tolerance test, in blood lipids, and in serum and adipose tissue expression of adipokines were not recuperated after WC. Moreover, the longer the HF feeding was (two, four and six months), more severe the adiposity was. After three consecutive WC, less marked was the BM reduction during SC feeding, while more severe was the BM increase during HF feeding. CONCLUSION: In conclusion, the results of the present study showed that both the HF diet and WC are relevant to BM evolution and fat pad remodeling in mice, with repercussion in blood lipids, homeostasis of glucose-insulin and adipokine levels. The simple reduction of the BM during a WC is not able to recover the high levels of adipokines in the serum and adipose tissue as well as the pro-inflammatory cytokines enhanced during a cycle of HF diet. These findings are significant because a milieu with altered adipokines in association with WC potentially aggravates the chronic inflammation attributed to dysregulated production and release of adipokines in mice.