Table 1 Preclinical evidence of anti-inflammatory adipokines in insulin resistance and atherogenic dyslipidemia

Adiponectin

Bovine aortic endothelial cells

–

Adiponectin has vascular action and stimulate the production of NO therefore causes vasodilation; possess anti-atherogenic properties

[105]

Rabbit

Renal artery

Treatment with Adiponectin decreases the atherosclerotic plaque size

[106]

Human aortic endothelial cells, human monocyte cell line

–

Adiponectin level is correlated with CAD risk

[107]

Human aortic endothelial cells

–

Adiponectin modulates the inflammatory response of endothelial cells via NF-kβ signaling through a cAMP-dependent pathway

[108]

Human umbilical vein endothelial cells

–

Protection of endothelial monolayer from angiotensin II, or TNF-induced hyper-permeability, modulation of microtubule and cytoskeleton stability via a cAMP/ PKA signaling cascade

[105]

HUVECs

–

Suppression of endothelial cell apoptosis, vascular protective activities

[110]

Ob/ob mice, ApoE-deficient Mice

–

Globular adiponectin (gAd) enhances fatty acid oxidation, ameliorate insulin resistance and atherosclerosis

[111]

Ob mice, wild type mice

Subcutaneous injection

Adiponectin replacement therapy attenuates myocardial damage in leptin-deficient mice

[112]

High-fat apolipoprotein E-deficient (ApoE − / −) mice

Via tail vein

Suppress oxidative stress, lipid production. Administration of adiponectin reduces atherosclerotic lesions formation size and rate in the aorta and reduces TC, TG, and LDL-c levels

[113]

Rats

Tail vein injection

Adiponectin alleviate the coronary no-reflow injury in T2DM rats by protecting endothelium and improving microcirculation

[114]

Adiponectin knockout mice or wild type mice

–

Adiponectin protects hearts from cardiac ischemia/reperfusion injury via inhibition of iNOS and nicotinamide adenine dinucleotide phosphate-oxidase protein expression and resultant oxidative/nitrative stress

[115]

C57BL/6 mice

Intraperitoneal injection

Adiponectin activates AMPK pathway, regulates glucose metabolism and insulin sensitivity in vitro and in vivo

[116]

. PPAR-γ + /– mice

Intraperitoneal injection

In insulin resistance the levels of adiponectin is decreased. Replenishment of adiponectin improves insulin sensitivity and diminishes diabetes

[117]

Adiponectin-deficient (APN-KO) mice

Adiponectin protects the heart from ischemia–reperfusion injury via AMPK- and COX-2–dependent mechanisms

[118]

Omentin-1

Cardiomyocyte

–

In T2D, omentin-1 level is decreased and Omentin-1 act as cardioprotective adipokine

[119]

Wistar rats

–

Omentin induces endothelium-dependent vaso-relaxation in rat isolated aorta via endothelium-derived NO through phosphorylation of eNOS

[120]

Wistar Rats

–

Omentin -1 level is modulated by AT during diabetes. Increased omentin-1 level interferes with the glucose metabolism pathway by stimulating phosphorylation of Akt in muscle tissue

[121]

Wistar rats, Cultured vascular smooth muscle cells

–

Omentin demonstrates anti-inflammatory effects, inhibits TNF-α induced VCAM. Omentin inhibits TNF-α-induced VCAM-1 expression via preventing the activation of p38 and JNK

[122]

Wistar Rats

Subcutaneous

Omentin-1 reduces blood pressure in rats via production of NO. Other anti-inflammatory adipokines such as adiponectin is increased following omentin-1 administration

[123]

Human Epicardial tissue

–

Circulating and epicardial AT-derived omentin-1 level decreased with patients with CAD

[124]

Human monocyte-derived macrophages, human aortic smooth muscle cells (HASMCs), and aortic lesions of Apoe-/- mice

Omentin-1 promotes anti-inflammatory M2 phenotype during differentiation of human monocytes into macrophages

Omentin-1 suppresses oxidized low-density lipoprotein-induced foam cell formation. Omentin-1 levels were markedly reduced in coronary endothelium and epicardial fat but increased in plasma and atheromatous plaques (macrophages/SMCs) in CAD patients compared with non-CAD patients

[125]

Thoracic aortas of C57BL/6 mice

–

Omentin-1 reversed impaired endothelial-dependent relaxations (EDR) in mouse aortas. Omentin-1 treatment reverses elevated ER stress markers, oxidative stress and reduction of NO production. Omentin-1 protects against high glucose-induced vascular endothelial dysfunction through inhibiting ER stress and oxidative stress and increasing NO production via activation of AMPK/PPAR-δ pathway

[126]

Apolipoprotein E-deficient (apoE-KO) mice

–

Omentin-1 act as anti-atherogenic adipokine that directly affects the phenotypes of macrophages

Omentin reduces the development of atherosclerosis by reducing inflammatory response of macrophages through the Akt-dependent mechanisms

[127]

SFRP5

Human adipocytes and skeletal muscle cells (hSkMC)

–

Sfrp5 lowered IL-6 release and NF-κβ phosphorylation in cytokine-treated human adipocytes

[128]

Mice

–

Sfrp5 have important roles in glucose regulation and β-cell function

[133]

3T3‐L1 pre‐adipocytes

–

Sfrp5 mRNA expression and protein secretion were increased during the differentiation of 3T3-L1 pre-adipocytes

Upregulation of Sfrp5 expression and secretion in adipocytes is one crucial mechanism by which rosiglitazone and metformin improve IR

[134]

Epicardial adipose tissue (EAT) and subcutaneous adipose tissue (SAT)

–

Sfrp5 mRNA levels were higher in EAT samples than in the paired SAT samples in both CAD and non-CAD group

Sfrp5 is secreted by visceral fat and that its local concentration in EAT may greatly exceed that in SAT

Low Sfrp5 and high Wnt5a levels are associated with the presence of CAD

[135]

Rat

–

Sfrp5 overexpression reverses the effects of microRNA-199a inhibitor on proliferation, migration, and cardiac fibroblast-to-myo fibroblast transformation of cardiac fibroblasts

[132]

Mice

–

Sfrp5 decreases the infarct size. Suppress pro-inflammatory Wnt5a/JNK signaling within the macrophages that infiltrate the infarct and pro-apoptotic Wnt5a/JNK signaling within myocytes

[123]

INS-1E cells

–

Sfrp5 reduces markers of cell proliferation, increases parallelly dose-dependently glucose-stimulated insulin secretion in INS-1E cells

[134]

CTRPs

Wistar Rats

–

CTRP3 protein expression levels are decreased in VAT at the pathogenic stages of insulin resistance and in T2DM

[135]

3T3-L1 adipocytes

–

CTRP12 improves the glucose metabolism 3T3-L1 adipocytes

[136]

C57BL/6 mice

–

CTRP12 have anti-diabetic actions that preferentially acts on adipose tissue and liver to control whole body glucose metabolism

[137]

CTRP1 transgenic (TG) mice

–

CTRP1 stimulated glucose uptake through the glucose transporter. GLUT4 translocation to the plasma membrane and also increased glucose consumption by stimulating glycolysis

[114]

Rats

Jugular vein injection

CTRP9 attenuates atrial inflammation and fibrosis via toll-like receptor 4/NF-κβ and Smad2/3 signaling pathways

[138]

Sprague–Dawley rats

Tail vein injection

CTRP3 protects cardiomyopathy via activating AMPKα pathway

[139]