Immunoproteasomal Inhibition With ONX-0914 Attenuates Atherosclerosis and Reduces White Adipose Tissue Mass and Metabolic Syndrome in Mice.

BACKGROUND: Atherosclerosis is the major underlying pathology of cardiovascular disease and is driven by dyslipidemia and inflammation. Inhibition of the immunoproteasome, a proteasome variant that is predominantly expressed by immune cells and plays an important role in antigen presentation, has been shown to have immunosuppressive effects. METHODS: We assessed the effect of ONX-0914, an inhibitor of the immunoproteasomal catalytic subunits LMP7 (proteasome subunit ß5i/large multifunctional peptidase 7) and LMP2 (proteasome subunit ß1i/large multifunctional peptidase 2), on atherosclerosis and metabolism in LDLr-/- and APOE*3-Leiden.CETP mice. RESULTS: ONX-0914 treatment significantly reduced atherosclerosis, reduced dendritic cell and macrophage levels and their activation, as well as the levels of antigen-experienced T cells during early plaque formation, and Th1 cells in advanced atherosclerosis in young and aged mice in various immune compartments. Additionally, ONX-0914 treatment led to a strong reduction in white adipose tissue mass and adipocyte progenitors, which coincided with neutrophil and macrophage accumulation in white adipose tissue. ONX-0914 reduced intestinal triglyceride uptake and gastric emptying, likely contributing to the reduction in white adipose tissue mass, as ONX-0914 did not increase energy expenditure or reduce total food intake. Concomitant with the reduction in white adipose tissue mass upon ONX-0914 treatment, we observed improvements in markers of metabolic syndrome, including lowered plasma triglyceride levels, insulin levels, and fasting blood glucose. CONCLUSIONS: We propose that immunoproteasomal inhibition reduces 3 major causes underlying cardiovascular disease, dyslipidemia, metabolic syndrome, and inflammation and is a new target in drug development for atherosclerosis treatment.

Regulation of host metabolic health by parasitic helminths.

Obesity is a worldwide pandemic and major risk factor for the development of metabolic syndrome (MetS) and type 2 diabetes (T2D). T2D requires lifelong medical support to limit complications and is defined by impaired glucose tolerance, insulin resistance (IR), and chronic low-level systemic inflammation initiating from adipose tissue. The current preventative strategies include a healthy diet, controlled physical activity, and medication targeting hyperglycemia, with underexplored underlying inflammation. Studies suggest a protective role for helminth infection in the prevention of T2D. The mechanisms may involve induction of modified type 2 and regulatory immune responses that suppress inflammation and promote insulin sensitivity. In this review, the roles of helminths in counteracting MetS, and prospects for harnessing these protective mechanisms for the development of novel anti-diabetes drugs are discussed.

Adipose failure through adipocyte overload and autoimmunity.

Metabolic syndrome poses a great worldwide threat to the health of the patients. Increased visceral adiposity is recognized as the main determinant of the detrimental clinical effects of insulin resistance. Inflammation and immune system activation in the adipose tissue (AT) have a central role in the pathophysiology of metabolic syndrome, but the mechanisms linking increased adiposity to immunity in the AT remain in part elusive. In this review, we support the central role of adipocyte overload and relative adipose failure as key determinants in triggering immune aggression to AT. This provides a mechanistic explanation of the relative metabolic wellness of metabolically normal obese people and the disruption in insulin signaling in metabolically obese lean people.

No association of natural killer cell number and function in peripheral blood with overweight/obesity and metabolic syndrome in a cohort of young women.

AIM: To reexamine the associations of NK cell number and function in the peripheral blood with overweight/obesity and the metabolic syndrome in a large, well-phenotyped human cohort. METHODS: Cross-sectional analysis of 273 women in the PPSDiab Study; measurement of absolute and relative number of NK cells in peripheral blood, and of functional parameters CD69 positivity and cytotoxicity against K562 cells; group comparison of NK cell characteristics between lean, overweight, and obese participants, as well as metabolic syndrome scores of 0, 1, 2, and ≥3; Spearman correlation analyses to clinical parameters related to the metabolic syndrome. RESULTS: We found no differences in NK cell number and function between lean, overweight, and obese women (relative NK cell number (median (Q1-Q3), [%]) 5.1(2.6-9.4) vs. 4.8 (2.9-8.4) vs. 3.8 (1.7-7.8), p = 0.187; absolute NK cell number [106 /L]: 86.9 (44.6-188.8) vs. 92.6 (52.5-154.6) vs. 85.9 (44-153.8), p = 0.632; CD69+ [%]: 27.2 (12.9-44.3) vs. 37.6 (13.2-52.8) vs. 33.6 (16.3-45), p = 0.136; cytotoxicity [%]: 11.0 (7.1-14.5) vs. 8.5 (6.4-13.2) vs. 11.3 (8.7-14.2), p = 0.094), as well as between different metabolic syndrome scores. Nonesterified fatty acids correlated with absolute and relative NK cell number and cytotoxicity (ρ [p-value]: 0.142 [0.021], 0.119 [0.049], and 0.131 [0.035], respectively). Relative NK cell number further correlated with high-density lipoprotein cholesterol (0.144 [0.018]) and cytotoxicity with 2 h glucose in oral glucose tolerance testing (0.132 [0.034]). CD69 positivity correlated with body fat (0.141 [0.021]), triglycerides (0.129 [0.033]), and plasma leptin (0.155 [0.010]). After correction for multiple testing, none of the associations remained significant. CONCLUSION: In the present study, we observed no associations of NK cell number and function in the peripheral blood with overweight/obesity and the metabolic syndrome. Extreme phenotypes of obesity and the metabolic syndrome might have caused differing results in previous studies. Further analyses with a focus on compartments other than peripheral blood may help to clarify the relation between NK cells and metabolic diseases.

Progress in the understanding of the pathophysiology of immunologic maladaptation related to early-onset preeclampsia and metabolic syndrome related to late-onset preeclampsia.

Among mammalian species, human reproduction has 2 outstanding features. The human hemochorial placentation is characterized by a very deep endovascular trophoblast invasion in the spiral arteries, reaching deep into the myometrium. This requires an agonistic direct cell-cell interaction between the maternal immune system and semiallogeneic trophoblast. The second feature is preeclampsia, a heterogeneous syndrome, a uniquely human condition. The human female is one of the few mammals exposed to her partner's semen on multiple occasions before conception. Regulatory T cells, especially paternal antigen-specific regulatory T cells, play an important role in the maintenance of pregnancy. Sexual intercourse increases the number of dendritic cells in the uterus that play an important role in the induction of paternal antigen-specific regulatory T cells. Paternal antigen-specific regulatory T cells maintain pregnancy by inducing tolerance. In the decidua basalis of preeclamptic cases, clonal regulatory T cells are reduced; these would normally monoclonally expand to recognize fetal or paternal antigens. Programmed cell death-1 expressed on T cells regulate cytotoxic T-cell activity and protect the fetus against maternal rejection. Programmed cell death-1 expression on clonal cytotoxic T cells is reduced in preeclampsia especially in early-onset preeclampsia, making the fetus and placenta vulnerable to attack by cytotoxic T cells. These phenomena can explain the epidemiologic phenomenon that preeclampsia is more common in couples using condom contraception, with shorter cohabitation periods, first pregnancies, first pregnancies in multiparous women when they change partner, and pregnancies after assisted reproduction using donated gametes. In contrast to its importance in early-onset preeclampsia, shallow trophoblast invasion does not play a role in the development of preeclampsia, that is, immune maladaptation does not seem to be involved. Late-onset preeclampsia (>34 weeks' gestation), representing 80% to 90% of preeclampsia in most developed countries with a "Western lifestyle," is strongly associated with maternal cardiometabolic variables (metabolic syndrome). Although the underlying pathophysiology might be quite different, syncytiotrophoblast stress is the final common pathway leading to the maternal syndrome among the subtypes of preeclampsia by causing an imbalance between proangiogenic factors (placental growth factor and vascular endothelial growth factor) and antiangiogenic factors (soluble fms-like tyrosine kinase-1 and soluble endoglin). Low-dose aspirin, started before 16 week's gestation, will prevent up to 60% of early-onset preeclampsia but will not prevent late-onset preeclampsia. Optimizing prepregnancy weight and controlling gestational weight gain may be the most effective ways to prevent preeclampsia.

Resveratrol and Immune Cells: A Link to Improve Human Health.

The use of polyphenols as adjuvants in lowering risk factors for various debilitating diseases has been investigated in recent years due to their possible antioxidant action. Polyphenols represent a fascinating and relatively new subject of research in nutraceuticals and nutrition, with interest rapidly expanding since they can help maintain health by controlling metabolism, weight, chronic diseases, and cell proliferation. Resveratrol is a phenolic compound found mostly in the pulp, peels, seeds, and stems of red grapes. It has a wide variety of biological actions that can be used to prevent the beginning of various diseases or manage their symptoms. Resveratrol can influence multiple inflammatory and non-inflammatory responses, protecting organs and tissues, thanks to its interaction with immune cells and its activity on SIRT1. This compound has anti-inflammatory, antioxidant, anti-apoptotic, neuroprotective, cardioprotective, anticancer, and antiviral properties, making it a potential adjunct to traditional pharmaceutical therapy in public health. This review aims to provide a comprehensive analysis of resveratrol in terms of active biological effects and mechanism of action in modifying the immune cellular response to promote human psychophysical health.

Targeting memory T cell metabolism to improve immunity.

Vaccination affords protection from disease by activating pathogen-specific immune cells and facilitating the development of persistent immunologic memory toward the vaccine-specific pathogen. Current vaccine regimens are often based on the efficiency of the acute immune response, and not necessarily on the generation of memory cells, in part because the mechanisms underlying the development of efficient immune memory remain incompletely understood. This Review describes recent advances in defining memory T cell metabolism and how metabolism of these cells might be altered in patients affected by mitochondrial diseases or metabolic syndrome, who show higher susceptibility to recurrent infections and higher rates of vaccine failure. It discusses how this new understanding could add to the way we think about immunologic memory, vaccine development, and cancer immunotherapy.

Antibodies against phosphorylcholine in hospitalized versus non-hospitalized obese subjects.

Obesity associates with reduced life expectancy, type 2 diabetes, hypertension and cardiovascular disease, and is characterized by chronic inflammation. Phosphorylcholine (PC) is an epitope on oxidized low-density lipoprotein, dead cells and some microorganisms. Antibodies against PC (anti-PC) have anti-inflammatory properties. Here, we explored the role of anti-PC in hospitalized versus non-hospitalized obese. One-hundred-and-twenty-eight obese (BMI ≥ 30 kg/m2) individuals (59.8 (± 5.5) years, 53.9% women) from the Malmö Diet and Cancer Cardiovascular Cohort were examined and IgM, IgG1 and IgG2 anti-PC were analyzed by ELISA. Individuals with at least one recorded history of hospitalization prior to study baseline were considered hospitalized obese (HO). Associations between IgM, IgG1 and IgG2 anti-PC and HO (n = 32)/non-hospitalized obese (NHO) (n = 96), but also with metabolic syndrome and diabetes were analysed using logistic regressions. Both IgM and IgG1 anti-PC were inversely associated with HO, also after controlling for age and sex. When further adjusted for waist circumference, systolic blood pressure, glucose levels and smoking status, only IgG1 anti-PC remained significantly associated with HO. In multivariate models, each 1 standard deviation of increment in anti-PC IgG1 levels was inversely associated with prevalence of HO (odds ratio 0.57; CI 95% 0.33-0.98; p = 0.044). IgG2 anti-PC did not show any associations with HO. Low levels of IgM and IgG1 anti-PC are associated with higher risk of being a HO individual independent of sex and age, IgG1 anti-PC also independently of diabetes and metabolic syndrome. The anti-inflammatory properties of these antibodies may be related to inflammation in obesity and its complications.

Metabolic disease and adverse events from immune checkpoint inhibitors.

OBJECTIVE: Obese and overweight body mass index (BMI) categories have been associated with increased immune-related adverse events (irAEs) in patients with cancer receiving immune checkpoint inhibitors (ICIs); however, the impact of being overweight in conjunction with related metabolic syndrome-associated factors on irAEs have not been investigated. We aimed to evaluate the impact of overweight and obese BMI according to metabolic disease burden on the development of irAEs. DESIGN AND METHODS: We conducted a retrospective observational study of patients receiving ICIs at a cancer center. Our main study outcome was development of ≥grade 2 (moderate) irAEs. Our main predictor was weight/metabolic disease risk category: (1) normal weight (BMI 18.5-24.9 kg/m2)/low metabolic risk (<2 metabolic diseases [diabetes, dyslipidemia, hypertension]), (2) normal weight/high metabolic risk (≥2 metabolic diseases), (3) overweight (BMI ≥25 kg/m2)/low metabolic risk, and (4) overweight/high metabolic risk. RESULTS: Of 411 patients in our cohort, 374 were eligible for analysis. Overall, 111 (30%) patients developed ≥grade 2 irAEs. In Cox analysis, overweight/low metabolic risk was significantly associated with ≥grade 2 irAEs (hazard ratio [HR]: 2.0, 95% confidence interval [95% CI]: 1.2-3.4) when compared to normal weight/low metabolic risk, while overweight/high metabolic risk (HR: 1.3, 95% CI: 0.7-2.2) and normal weight/high metabolic risk (HR: 1.5, 95% CI: 0.7-3.0) were not. CONCLUSIONS: Overweight patients with fewer metabolic comorbidities were at increased risk for irAEs. This study provides an important insight that BMI should be evaluated in the context of associated metabolic comorbidities in assessing risk of irAE development and ICI immune response.

Effects of Morbid Obesity and Metabolic Syndrome on the Composition of Circulating Immune Subsets.

Morbid obesity is characterized by chronic, low-grade inflammation, which is associated with 'inflamm-aging'. The presence of metabolic syndrome (MetS) might accelerate this phenomenon of metaflammation. In this study, we assessed the effects of morbid obesity and MetS on the composition of a broad spectrum of immune cells present within the circulation. A total of 117 morbidly obese patients (MOP) without MetS (MetS-), 127 MOP with MetS (MetS+) and 55 lean controls (LC) were included in this study. Absolute numbers of T cell, B cell, NK cell and monocyte subsets were assessed within peripheral blood using flow cytometry. Both absolute cell numbers and proportion of cells were evaluated correcting for covariates age, body mass index and cytomegalovirus serostatus. Although the absolute number of circulating CD4+ T cells was increased in the MetS+ group, the CD4+ T cell composition was not influenced by MetS. The CD8+ T cell and B cell compartment contained more differentiated cells in the MOP, but was not affected by MetS. Even though the absolute numbers of NK cells and monocytes were increased in the MOP as compared to LC, there was no difference in proportions of NK and monocyte subsets between the three study groups. In conclusion, although absolute numbers of CD4+ and CD8+ T cells, B cells, NK cells and monocytes are increased in MOP, obesity-induced effects of the composition of the immune system are confined to a more differentiated phenotype of CD8+ T cells and B cells. These results were not affected by MetS.

A Positive Association of Overactivated Immunity with Metabolic Syndrome Risk and Mitigation of Its Association by a Plant-Based Diet and Physical Activity in a Large Cohort Study.

The association between immunity and metabolic syndrome (MetS) has been studied, but its interaction with lifestyles remains unclear. We studied their association and interactions with lifestyles in 40,768 adults aged over 40 years from a large-scale, hospital-based cohort study collected during 2010-2013. White blood cell counts (WBC) and serum C-reactive protein concentrations (CRP) were used as indexes of immune status. The participants were categorized into four groups by the cutoff points of 6.2 × 109/L WBC(L-WBC) and <0.5 mg/dL CRP(L-CRP): L-WBC+L-CRP(n = 25,604), H-WBC+L-CRP(n = 13,880), L-WBC+H-CRP(n = 464), and H-WBC+H-CRP(n = 820). The participants in the H-WBC+L-CRP were younger and had higher numbers of males than the L-WBC+L-CRP. MetS risk was higher by 1.75- and 1.86-fold in the H-WBC+L-CRP and H-WBC+H-CRP, respectively, than the L-WBC+L-CRP. MetS components, including plasma glucose and triglyceride concentrations, and SBP were elevated in H-WBC+L-CRP and H-WBC+H-CRP compared with L-WBC+L-CR+P. The risk of hyperglycemia and high HbA1c was the highest in the H-WBC+H-CRP among all groups. Areas of WBC counts and serum CRP concentrations were 0.637 and 0.672, respectively, in the receiver operating characteristic curve. Daily intake of energy, carbohydrate, protein, and fat was not significantly different in the groups based on WBC counts and CRP. However, a plant-based diet (PBD), physical activity, and non-smoking were related to lowering WBC counts and CRP, but a Western-style diet was linked to elevating CRP. A high PBD intake and smoking status interacted with immunity to influence MetS risk: a low PBD and current smoking were associated with a higher MetS risk in the H-WBC+H-CRP. In conclusion, overactivated immunity determined by CRP and WBC was associated with MetS risk. Behavior modification with PBD and physical activity might be related to immunity regulation.

Association between Polygenetic Risk Scores of Low Immunity and Interactions between These Scores and Moderate Fat Intake in a Large Cohort.

White blood cell (WBC) counts represent overall immunity. However, a few studies have been conducted to explore the genetic impacts of immunity and their interaction with lifestyles. We aimed to identify genetic variants associated with a low-WBC risk and document interactions between polygenetic risk scores (PRS), lifestyle factors, and nutrient intakes that influence low-WBC risk in a large hospital-based cohort. Single nucleotide polymorphisms (SNPs) were selected by genome-wide association study of participants with a low-WBC count (<4 × 109/L, n = 4176; low-WBC group) or with a normal WBC count (≥4 × 109/L, n = 36,551; control group). The best model for gene-gene interactions was selected by generalized multifactor dimensionality reduction. PRS was generated by summing selected SNP risk alleles of the best genetic model. Adjusted odds ratio (ORs) of the low-WBC group were 1.467 (1.219-1.765) for cancer incidence risk and 0.458 (0.385-0.545) for metabolic syndrome risk. Vitamin D intake, plant-based diet, and regular exercise were positively related to the low-WBC group, but smoking and alcohol intake showed an inverse association. The 7 SNPs included in the best genetic model were PSMD3_rs9898547, LCT_rs80157389, HLA-DRB1_rs532162239 and rs3097649, HLA-C rs2308575, CDKN1A_rs3176337 and THRA_rs7502539. PRS with 7 SNP model were positively associated with the low-WBC risk by 2.123-fold (1.741 to 2.589). PRS interacted with fat intake and regular exercise but not with other nutrient intakes or lifestyles. The proportion with the low WBC in the participants with high-PRS was lower among those with moderate-fat intake and regular exercise than those with low-fat intake and no exercise. In conclusion, adults with high-PRS had a higher risk of a low WBC count, and they needed to be advised to have moderate fat intake (20-25 energy percent) and regular exercise.

Anti-COVID-19 measurements for hidradenitis suppurativa patients.

The reported incidence of COVID-19 among cohorts of patients with inflammatory bowel and skin diseases under treatment with biologicals is low. Treatment may further modify disease severity as some biological modifiers, such as anakinra, are also proposed for the management of COVID-19 patients potentially providing HS patients with an advantage. The above preliminary evidence suggests that hidradenitis suppurativa (HS) does probably not provide an increased susceptibility for COVID-19 and that any susceptibility is unlikely to be modified negatively by treatment with biologicals. On the occasion of its 10th International Conference, experts of the European Hidradenitis Suppurativa Foundation e.V. have prepared a consensus statement regarding anti-COVID-19 measurements for HS patients. Based on the available knowledge, patients with HS may be vaccinated against SARS-CoV2 and patients affected by metabolic syndrome constitute a high-risk group for COVID-19 and should be vaccinated at the earliest convenient point in time. HS patients on treatment with adalimumab can be vaccinated with non-living virus anti-SARS-CoV2 vaccines. A possible suboptimal effect of the vaccine may be suspected but might not be expected universally. The management of the biological treatment in HS patients is at the discretion of the dermatologist / responsible physician.

Insulin resistance is linked to a specific profile of immune activation in human subjects.

We tested the hypothesis that a particular immune activation profile might be correlated with insulin resistance in a general population. By measuring 43 markers of immune, endothelial, and coagulation activation, we have previously shown that five different immune activation profiles may be distinguished in 150 volunteers. One of these profiles, Profile 2, characterized by CD4+ T cell senescence, inflammation, monocyte, B cell, and endothelial activation, presented elevated insulinemia, glycemia, triglyceridemia, and γ-glutamyl transferase, a marker of liver injury, in comparison with other profiles. Our data are compatible with a model in which a particular immune activation profile might favor the development of insulin resistance and metabolic syndrome. In this hypothesis, identification of this profile, that is feasible with only 3 markers with an error rate of 5%, might allow to personalize the screening and prevention of metabolic syndrome-driven morbidities as liver steatosis.

The role of the microbiome in gastrointestinal inflammation.

The microbiome plays an important role in maintaining human health. Despite multiple factors being attributed to the shaping of the human microbiome, extrinsic factors such diet and use of medications including antibiotics appear to dominate. Mucosal surfaces, particularly in the gut, are highly adapted to be able to tolerate a large population of microorganisms whilst still being able to produce a rapid and effective immune response against infection. The intestinal microbiome is not functionally independent from the host mucosa and can, through presentation of microbe-associated molecular patterns (MAMPs) and generation of microbe-derived metabolites, fundamentally influence mucosal barrier integrity and modulate host immunity. In a healthy gut there is an abundance of beneficial bacteria that help to preserve intestinal homoeostasis, promote protective immune responses, and limit excessive inflammation. The importance of the microbiome is further highlighted during dysbiosis where a loss of this finely balanced microbial population can lead to mucosal barrier dysfunction, aberrant immune responses, and chronic inflammation that increases the risk of disease development. Improvements in our understanding of the microbiome are providing opportunities to harness members of a healthy microbiota to help reverse dysbiosis, reduce inflammation, and ultimately prevent disease progression.

The Role of the Gut-Liver Axis in Metabolic Dysfunction-Associated Fatty Liver Disease.

The complex interplay between the gut microbiota, the intestinal barrier, the immune system and the liver is strongly influenced by environmental and genetic factors that can disrupt the homeostasis leading to disease. Among the modulable factors, diet has been identified as a key regulator of microbiota composition in patients with metabolic syndrome and related diseases, including the metabolic dysfunction-associated fatty liver disease (MAFLD). The altered microbiota disrupts the intestinal barrier at different levels inducing functional and structural changes at the mucus lining, the intercellular junctions on the epithelial layer, or at the recently characterized vascular barrier. Barrier disruption leads to an increased gut permeability to bacteria and derived products which challenge the immune system and promote inflammation. All these alterations contribute to the pathogenesis of MAFLD, and thus, therapeutic approaches targeting the gut-liver-axis are increasingly being explored. In addition, the specific changes induced in the intestinal flora may allow to characterize distinctive microbial signatures for non-invasive diagnosis, severity stratification and disease monitoring.

Association between Toxoplasma gondii infection and metabolic syndrome in obese adolescents: A possible immune-metabolic link.

Background Toxoplasmosis as a global disease is considered as a triggering factor responsible for development of several clinical diseases. However, Toxoplasma gondii (T. gondii) is an understudied parasite of potential interest in obesity research. The current study aimed to explore the role of latent T. gondii infection in the pathogenesis of metabolic syndrome (MetS) in obese adolescents through studying the relationship between serum interferon-gamma [IFN-γ] and serum chemerin in context of MetS components. Methods Eighty-three obese adolescents were serologically screened for T. gondii-IgG antibodies and compared to 35 age-matched healthy T. gondii-seronegative controls. Participants were evaluated for anthropometric measurements, total-fat mass [FM], trunk-FM, serum lipid profile, IFN-γ, and chemerin levels. Homeostatic Model Assessment of insulin resistance (HOMA-IR) was calculated. Results The prevalence of MetS was significantly higher within obese T. gondii-seropositive group compared to obese T. gondii-seronegative group (P = 0.033). Seropositive obese MetS group displayed significantly higher trunk-FM, HOMA-IR, chemerin, and IFN-γ compared to seronegative obese MetS group. Serum chemerin and IFN-γ were strongly correlated (P < 0.001) and were positively correlated with BMI, WC, total-FM, trunk-FM, HOMA-IR, cholesterol, triglycerides and negatively correlated with HDLC. HOMA-IR was a common predictor for serum chemerin (P = 0.030) and IFN-γ (P < 0.001). Conclusions The study results suggest that T. gondii infection may exert an immune-metabolic effect that may have a potential role in the development of MetS among obese adolescents.

Anti-inflammatory effects of diet and caloric restriction in metabolic syndrome.

BACKGROUND: Weight loss in patients with metabolic syndrome has positive effects on cardiovascular and type 2 diabetes risks, but its effects on peripheral cytokines and lipid profiles in patients are still unclear. AIM: To determine the effects of diet-induced weight loss on metabolic parameters, lipids and cytokine profiles. METHODS: Eighteen adult males with metabolic syndrome (defined according to IDF 2009) and Body Mass Index (BMI) between 25 and 35 kg/m2 were subjected to a balanced hypocaloric diet for 6 months to reach at least a 5% body weight loss. RESULTS: After weight loss, a significant improvement in BMI, waist circumference, insulin, fasting blood glucose and HOMA-IR (homeostasis model assessment of insulin resistance) was observed. The analysis of LDL (low-density lipoprotein cholesterol) and HDL (high-density lipoprotein cholesterol) lipoproteins showed a change in their composition with a massive transfer of triacylglycerols from HDL to LDL. This was associated with a significant reduction in peripheral pro-inflammatory cytokines such as IL-6, TNF-α, IL-8 and MIP-1ß, leading to an overall decreased inflammatory score. An interesting positive correlation was also observed among peripheral cytokines levels after diet and peripheral levels of CETP (cholesteryl ester transfer protein), an enzyme with a key role in lipid change. CONCLUSION: Weight loss through caloric restriction is associated with an improvement in peripheral lipid and cytokine profiles that may play a major role in improving cardiovascular risk.

Dangerous liaisons? The role of inflammation and comorbidities in HIV and SARS-CoV-2 infection.

INTRODUCTION: In people living with HIV (PLWH), immune activation and inflammation levels are high even when viral suppression is maintained, potentially contributing to several comorbidities, and hampering the immune response to infections such as the recent SARS-CoV-2 disease 2019 (COVID-19). AREAS COVERED: Immune activation and inflammation play a role in SARS-CoV-2 infection. Severe COVID-19 patients may experience cytokine release syndrome (CRS), leading to alveolar damage, pulmonary fibrinolysis, dysregulated coagulation, and pulmonary injury. Into the systemic circulation, cytokines in excess might leak out of pulmonary circulation, causing systemic symptoms and possibly a multiple-organ dysfunction syndrome. Preexisting comorbidities are also linked to worse COVID-19 outcome: studies suggest that diabetes and hypertension are linked to higher mortality rates. Such comorbidities are more frequent in PLWH, but it is unclear if they have worse outcomes in the case of COVID-19. The literature was searched in PubMed/MEDLINE and EMBASE, and manually in COVID-19 resources. EXPERT OPINION: A body of evidence shows that HIV and SARS-CoV-2 are able to activate inflammatory pathways, acute in the case of SARS-CoV-2, chronic in the case of HIV, while the comorbidities seem to represent, in the first case, a contributory cause, in the second an effect of the virus-induced damage.

Psoriasis in Patients with Metabolic Syndrome or Type 2 Diabetes Mellitus: Treatment Challenges.

Psoriasis is a chronic inflammatory disease that affects 2-3% of the population worldwide. It is associated with plaques, psoriatic arthritis, and metabolic syndrome and its components, including obesity, diabetes, dyslipidemia, nonalcoholic fatty liver disease, and cardiovascular disease. In this review, we highlight the shared pathogenic pathways leading to the comorbid existence of both diseases and the impact of drugs used for psoriasis on metabolic syndrome and vice versa. Persistent inflammation is common to both diseases. They share increased inflammatory cytokines such as tumor necrosis factor (TNF)-α and interleukin-6. Biologics have revolutionized the treatment of plaque psoriasis and also have a positive impact on metabolic syndrome. There is some evidence that TNFα inhibitors decrease insulin resistance and improve glycemic indices. Some psoriasis treatments may result in decreased body weight. Lifestyle measures used in the management of metabolic syndrome, such as weight loss, exercise, and healthy diet, are beneficial in patients with psoriasis. Considering the association between metabolic syndrome and psoriasis, we recommend screening patients with psoriasis for metabolic syndrome with clinical examinations and laboratory tests. Patients with a co-diagnosis of these diseases deserve special attention for optimal treatment.