AIM
Serum γ-glutamyltransferase (GGT) is used as a marker of hepatic dysfunction. Recently, several studies reported that GGT is significantly associated with cardiovascular mortality and atherosclerosis. Adiponectin is known to play an important role in the development of atherosclerosis, but its physiologic role has yet to be fully determined. In this study, we investigated the relationships among serum GGT, adiponectin and arterial stiffness.


METHODS
Of 4236 subjects recruited from 17 different medical centers in Seoul, Korea, 2846 subjects were enrolled in our study. The parameters of metabolic syndrome (MetS) were assessed in these subjects, and their plasma adiponectin levels and pulse wave velocity (PWV) were measured along with anthropometric and biochemical profiles, including GGT.


RESULTS
The subjects were stratified into 3 groups according to GGT values. PWV values gradually increased and the adiponectin level decreased with GGT tertiles. Aortic PWV showed a significant correlation with age, SBP, FPG, but there was no correlation among aortic PWV, GGT and adiponectin. Peripheral PWV demonstrated a significant correlation with age, SBP, DBP, BMI, WC, FPG and GGT, but there was no correlation between peripheral PWV and adiponectin. In multiple logistic regression analysis after adjusting for risk factors, GGT was a significant contributor to increased peripheral PWV.


CONCLUSIONS
These findings indicate that serum GGT is independently associated with increased arterial stiffness, but there was no correlation between adiponectin and arterial stiffness in both males and females.

https://ir.ymlib.yonsei.ac.kr/bitstream/22282913/90618/1/T201203068.pdf

Association between γ-glutamyltransferase, adiponectin and arterial stiffness

Bariatric surgery is considered to be the most effective treatment option for weight reduction in obese patients. Abdominal obesity is frequently accompanied by metabolic syndrome (MS). Adipokines are cell signaling proteins that have direct impact upon the metabolic homeostasis. The purpose of this analysis was to evaluate the effect of bariatric surgery, including laparoscopic sleeve gastrectomy (LSG) and laparoscopic gastric bypass (LRYGB) on the adipokine levels and metabolic profile as well as MS and status of type 2 diabetes (T2D).We analyzed anthropometric parameters, blood levels of adipokines, vitamins, lipids and inflammatory markers in 30 bariatric surgery patients with obesity of class II or III 1 month before and 1 year after surgery as well as in 60 obese patients from general practice (GP) and 15 patients with normal body mass (control).The BMI was significantly higher among patients before surgery and GP patients in comparison to control and post-surgery patients. The levels of glucose, cholesterol and LDL-cholesterol, triglyceride and hs-CRP were the highest in patients before surgery but decreased significantly after surgery, while the level of HDL-cholesterol increased after surgery. The levels of adiponectin increased and that of leptin decreased after surgery. The significant difference in the concentration of resistin was revealed between LSG and LRYGB methods. The relationship between resistin and vitamin D was also found. The patients with MS and T2D displayed significantly greater reduction in lipid markers and adipokine levels than the rest of patients.Remarkable changes in levels of adipokines after bariatric surgery appear like increase in adiponectin and decrease in leptin levels. Significant improvement in anthropometric parameters, metabolic and inflammatory markers occurs, suggesting high potential for reduction of metabolic syndrome and risk for type 2 diabetes. We have shown for the first time ever that level of vitamin D may be involved in resistin regulation. 

https://bmcendocrdisord.biomedcentral.com/counter/pdf/10.1186/s12902-022-00942-7

Changes in adipokine levels and metabolic profiles following bariatric surgery

Psoriasis is a chronic and immune-mediated skin condition characterized by pro-inflammatory cytokines and keratinocyte hyperproliferation. Dendritic cells, T lymphocytes, and keratinocytes represent the main cell subtypes involved in the pathogenesis of psoriasis, while the interleukin-23 (IL-23)/IL-17 pathway enhances the disease progression. Human adipose tissue is an endocrine organ, which secretes multiple proteins, known as adipokines, such as adiponectin, leptin, visfatin, or resistin. Current evidence highlights the immunomodulatory roles of adipokines, which may contribute to the progression or suppression of psoriasis. A better understanding of the complexity of psoriasis pathophysiology linked with adipokines could result in developing novel diagnostic or therapeutic strategies. This review aims to present the pathogenesis of psoriasis and the roles of adipokines in this process.

/pdf/the-role-of-adipokines-in-the-pathogenesis-of-psoriasis-2coebu1a.pdf

The Role of Adipokines in the Pathogenesis of Psoriasis

Medin, a small 50-amino acid peptide, is an internal cleaved product from the second discoidin domain of milk fat globule epidermal growth factor VIII (MFG-E8) protein. Medin has been reported as the most common amylogenic protein in the upper part of the arterial system, including aortic, temporal, and cerebral arterial walls in the elderly. Medin has a high affinity to elastic fibers and is closely associated with arterial degenerative inflammation, elastic fiber fragmentation, calcification, and amyloidosis. In vitro, treating with the medin peptide promotes the inflammatory phenotypic shift of both endothelial cells and vascular smooth muscle cells. In vitro, ex vivo, and in vivo studies demonstrate that medin enhances the abundance of reactive oxygen species and reactive nitrogen species produced by both endothelial cells and vascular smooth muscle cells and promotes vascular endothelial dysfunction and arterial stiffening. Immunostaining and immunoblotting analyses of human samples indicate that the levels of medin are increased in the pathogenesis of aortic aneurysm/dissection, temporal arteritis, and cerebrovascular dementia. Thus, medin peptide could be targeted as a biomarker diagnostic tool or as a potential molecular approach to curbing the arterial degenerative inflammatory remodeling that accompanies aging and disease.

/pdf/milk-fat-globule-epidermal-growth-factor-viii-fragment-medin-cwsy44ir.pdf

Milk Fat Globule Epidermal Growth Factor VIII Fragment Medin in Age-Associated Arterial Adverse Remodeling and Arterial Disease

Objective Adipokines, such as adiponectin and chemerin, regulate fat metabolism and are critical for the development of atherosclerosis. Investigating the correlations of adiponectin and chemerin with atherosclerosis in older adults with type 2 diabetes mellitus (T2DM) will shed light on the search for new markers for early diagnosis of diabetic atherosclerosis. Methods A total of 120 older T2DM patients and nine healthy controls were enrolled in this study. The clinical parameters, such as brachial-ankle pulse wave velocity (ba-PWV), adiponectin, and chemerin, were examined and recorded. T2DM subjects were divided into three groups according to ba-PWV level (high, medium, or low). The data were processed and analyzed by identical methods. Results Significantly higher chemerin and lower adiponectin levels were detected in the plasma of T2DM patients than in healthy controls. The plasma levels of chemerin and adiponectin were negatively correlated in T2DM patients. Moreover, chemerin and adiponectin were significantly correlated with body mass index, ankle-brachial index, insulin, and ba-PWV. Multiple linear regression analysis revealed that chemerin and adiponectin were independently affecting ba-PWV. Conclusion Adiponectin and chemerin are potential markers for diagnosis and monitoring of early stage of atherosclerosis in older adults with T2DM. Further clinical investigations are required to confirm these markers.

Plasma levels of adiponectin and chemerin are associated with early stage of atherosclerosis in older adults with type 2 diabetes mellitus.

Vascular calcification/aging is a crucial feature of diabetic macro vasculopathy, resulting in serious cardiovascular diseases. The calcification/senescence of vascular smooth muscle cells (VSMCs) induced by hyperglycemia can cause diabetic vascular calcification/aging. However, the mechanism of VSMCs calcification/senescence involved in diabetic vascular calcification/aging remains unknown. The purpose of this study was to determine how the high glucose (HG) information in circulating blood is transmitted from vascular endothelial cells (ECs) to VSMCs, which are not contacted with blood directly. Exosomes have attracted much attention for their vital roles in regulating cell-to-cell communication. In this study, we found that milk fat globule epidermal growth factor 8 (MFGE8) was enriched in high glucose induced human umbilical vein endothelial cell exosomes (HG-HUVEC-Exo) and regulate VSMCs calcification/senescence, characterized by up-regulated expressions of alkaline phosphatase (ALP) and Runt-related transcription factor 2 (Runx2), as well as the increased mineralized nodules and senescence-associated {beta}-galactosidase (SA-{beta}-gal) positive cells. Upstream mechanism studies showed that sirtuin1 (SIRT1) was involved in VSMCs calcification/senescence by affecting the expression of MFGE8. We also found that inflammatory response mediated by IL-1{beta}, IL-6, and IL-8 was closely associated with MFGE8 and played a key role in regulating HG-HUVEC-Exo-induced VSMCs calcification/senescence. These findings provide a new insight into the mechanism of exosomal MFGE8 as a potential preventive and therapeutic target for the intervention of diabetic vascular calcification/aging.

/pdf/exosomal-mfge8-from-high-glucose-induced-endothelial-cells-4jn6kcpauw.pdf

Hua-Hua Li

Papers

Plasma levels of adiponectin and chemerin are associated with early stage of atherosclerosis in older adults with type 2 diabetes mellitus.

Exosomal MFGE8 from high glucose induced endothelial cells is involved in calcification/senescence of vascular smooth muscle cells