Low-grade Systemic Inflammatory Condition Research Articles

Is there a role for essential fatty acids in osteoporosis?

Inflammatory markers are inversely associated with bone density, geometry, and strength in postmenopausal women, and elderly subjects suggesting that osteoporosis is a low-grade systemic inflammatory condition. But glucocorticoids that are potent anti-inflammatory compounds instead of arresting/preventing osteoporosis induce osteoporosis. These results indicate that IL-6 and TNF-α, post-menopausal state, and steroids produce osteoporosis by an unidentified mechanism. Pro-inflammatory cytokines, estrogen, and steroids bring about their actions by influencing the metabolism of essential fatty acids (EFAs). I propose that EFAs and their metabolites act as second messengers of actions of corticosteroids, cytokines, and estrogen. This implies that EFAs are of benefit in the prevention and management of osteoporosis. This argument is supported by the observation that plasma phospholipid content of unsaturated fatty acids is decreased in those with osteoporosis. The reports that long-chain metabolites of EFAs including arachidonic acid, docosahexaenoic acid and eicosapentaenoic acid, and lipoxin A4 are of benefit in the prevention and management of osteoporosis lends further support to this proposal.

Capsaicin: A Potential Treatment to Improve Cerebrovascular Function and Cognition in Obesity and Ageing.

Impaired cognition is the primary symptom of dementia, which can lead to functional disability and reduced quality of life among an increasingly ageing population. Ageing is associated with increased oxidative stress, chronic low-grade systemic inflammation, and endothelial dysfunction, which reduces cerebrovascular function leading to cognitive decline. Chronic low-grade systemic inflammatory conditions, such as obesity, exacerbate this decline beyond normal ageing and predispose individuals to neurodegenerative diseases, such as dementia. Capsaicin, the major pungent molecule of chilli, has recently demonstrated improvements in cognition in animal models via activation of the transient receptor potential vanilloid channel 1 (TRPV1). Capsaicin-induced TRPV1 activation reduces adiposity, chronic low-grade systemic inflammation, and oxidative stress, as well as improves endothelial function, all of which are associated with cerebrovascular function and cognition. This review examines the current literature on capsaicin and Capsimax, a capsaicin supplement associated with reduced gastrointestinal irritation compared to capsaicin. Acute and chronic capsaicin treatment can improve cognition in animals. However, studies adequately assessing the effects of capsaicin on cerebrovascular function, and cognition in humans do not exist. Capsimax may be a potentially safe therapeutic intervention for future clinical trials testing the effects of capsaicin on cerebrovascular function and cognition.

Effects of anti-inflammatory and adaptogenic herbal extracts on gene expression of eicosanoids signaling pathways in isolated brain cells

IntroductionThe adaptogens modulate expression of genes playing key roles in development of aging-related disorders, which are considered as low-grade systemic inflammatory conditions characterized by an imbalance between pro-and anti-inflammatory eicosanoids. Aim of the StudyWe compared the effects of anti-inflammatory and adaptogenic plant extracts on the expression of genes involved in biosynthesis of eicosanoids with the purpose to find those plants, which selectively upregulated the expression of anti-inflammatory lipoxins signaling pathways and inhibited pro-inflammatory signaling pathways associated with biosynthesis of leukotrienes, prostaglandins and thromboxanes. Materials and MethodsWe conducted transcriptome-wide RNA sequencing to profile gene expression alterations in T98G neuroglia cells upon treatment of plant extract and analyzed the relevance of deregulated genes to eicosanoids signaling pathways using in silico models. ResultsFor the first time, we demonstrated that Rhodiola rosea, Withania somnifera and Eleutherococcus senticosus downregulate the expression of key genes (ALOX5AP, DPEP2, LTC4S) involved biosynthesis of leukotrienes A, B, C, D and E, resulting in inhibition of leukotriene signaling pathway suggesting their potential benefits in Alzheimer disease. The common feature for all tested anti-inflammatory plants extracts was related to downregulation of ALOX12, which was also associated with neuroprotective action of these medicinal plants as well as their potential benefits in neurodegenerative diseases. None of tested anti-inflammatory and adaptogenic plants selectively activated the ALOX15-mediated signaling pathway, which is associated with generation anti-inflammatory lipoxins. Almost all tested plants upregulated the expression of the prostaglandin E receptor 3 gene (PTGER3) suggesting their potential benefits in the treatment of cancer. ConclusionEvery single plant tested in this study revealed a specific “signature” on eicosanoid signaling-related gene expression, regardless of their common features as anti-inflammatory or adaptogenic activity. Further studies of the combination of Rhodiola with Withania (Adaptra) for the treatment of Alzheimer disease are required.

Amelioration of streptozotocin-induced type 2 diabetes mellitus in Wistar rats by arachidonic acid

Traditionally arachidonic acid (AA, 20:4 n-6) is considered as a pro-inflammatory molecule since it forms precursor to prostaglandins (PGs), leukotrienes (LTs) and thromboxanes (TXs) that have pro-inflammatory actions. Type 2 diabetes mellitus (type 2 DM) is considered as a low-grade systemic inflammatory condition in which circulating PGs and LTs are increased. Streptozotocin (STZ)-induced type 2 DM is used as a model of human type 2 DM in which peripheral insulin resistance, increased plasma interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) and hyperglycemia occurs. In the present study, we observed that oral supplementation of AA prevented STZ-induced type 2 DM in Wistar rats by restoring hyperglycemia, plasma levels of TNF-α and IL-6; adipose tissue NF-kB and lipocalin 2 (LPCLN2) and pancreatic tissue NF-kB and 5- and 12- lipoxygenase enzymes to normal. AA treatment enhanced insulin sensitivity and plasma lipoxin A4 (LXA4) levels, a potent anti-inflammatory molecule derived from AA. These results are supported by our previous studies wherein it was noted that plasma phospholipid content of AA and circulating LXA4 levels are low in those with type 2 DM. In a preliminary study, we also noted that high-fat-diet (HFD)-induced type 2 DM in Wistar rats can be prevented by oral supplementation of AA. These results suggest AA has anti-inflammatory and anti-diabetic actions by enhancing the production of its anti-inflammatory metabolite LXA4.

Progression of Time-Dependent Changes to the Mechanisms of Vasodilation by Protease-Activated Receptor 2 in Metabolic Syndrome.

Protease-activated receptor 2 (PAR2) is a G protein-coupled receptor activated by serine proteases released from tissues or by synthetic peptide ligands administered pharmacologically. Its wide expression in the cardiovascular system, particularly within the endothelium, vasodilation activity, and link to increased expression of inflammatory cytokines positions PAR2 as a potentially important regulator of vascular pathology under conditions of tissue inflammation, and injury; and thus, a pharmaceutical target for new therapeutics. Obesity is considered a chronic low-grade systemic inflammatory condition as inflammatory cytokines released from adipocytes are closely related to development of metabolic syndrome and related disorders. Our work over the past five-years has focused on the changes in vasomotor functions of PAR2 in metabolic syndrome, using an animal model known as the SHRSP.Z-Leprfa/IzmDmcr rats (SHRSP.ZF). In young SHRSP.ZF that had already developed impaired responses to nitric oxide, we reported that PAR2-induced endothelium-dependent vasodilation is preserved. However, this PAR2 vasodilation decreased with increasing age and further chronic exposure to the conditions of metabolism disorder. These findings raise the possibility that PAR2 regulates tissue perfusion and can protect organs from injury, which is an increasing clinical concern at later stages of metabolic syndrome. Here we present our studies on the time-dependent changes in vasoreactivity to PAR2 in metabolic syndrome and the underlying mechanisms. Furthermore, we discuss the implications of these age-related changes in PAR2 for the cardiovascular system in metabolic syndrome.

Airway Hyperresponsiveness to Mannitol in Obesity Before and After Bariatric Surgery.

BackgroundThe relationship between airway hyperresponsiveness (AHR) and obesity, a low-grade systemic inflammatory condition, remains largely unknown. It is established that AHR to indirect stimuli is associated with active airway inflammation. The objectives were to investigate the rate of AHR to mannitol in obese subjects and its changes 1 year after bariatric surgery (BS).MethodsWe enrolled 58 candidates to BS severely obese (33 nonsmokers and 25 smokers) without history of asthma and 20 healthy, nonobese participants and related AHR to functional findings and serum and exhaled biomarkers.ResultsBefore surgery, AHR was observed in 16 (28 %) obese with the provocation doses of mannitol to induce a 15 % fall in FEV1 (PD15) of (geometric mean [95 % CI]) 83 (24–145) mg. Compared to control participants, obese participants had lower spirometric values and higher serum and exhaled biomarkers (p < 0.05 each). After surgery, AHR was abolished (p < 0.01) in all but four obese subjects.ConclusionsWeight loss induced by BS was the key independent factor associated to AHR improvement. AHR to mannitol is highly prevalent in obesity, and it is largely abolished by BS.

Non-steroidal anti-inflammatory drugs attenuate the vascular responses in aging metabolic syndrome rats.

Metabolic syndrome (MS) and aging are low-grade systemic inflammatory conditions, and inflammation is a key component of endothelial dysfunction. The aim of this study was to investigate the effects of non-steroidal anti-inflammatory drugs (NSAIDs) upon the vascular reactivity in aging MS rats. MS was induced in young male rats by adding 30% sucrose in drinking water over 6, 12, and 18 months. When the treatment was finished, the blood samples were collected, and aortas were dissected out. The expression of COX isoenzymes and PLA2 in the aortas was analyzed using Western blot analysis. The contractile responses of aortic rings to norepinephrine (1 μmol/L) were measured in the presence or absence of different NSAIDs (10 μmol/L for each). Serum levels of pro-inflammatory cytokines (IL-6, TNF-α, and IL-1β) in control rats were remained stable during the aging process, whereas serum IL-6 in MS rats were significantly increased at 12 and 18 months. The levels of COX isoenzyme and PLA2 in aortas from control rats increased with the aging, whereas those in aortas from MS rats were irregularly increased with the highest levels at 6 months. Pretreatment with acetylsalicylic acid (a COX-1 preferential inhibitor), indomethacin (a non-selective COX inhibitor) or meloxicam (a COX-2 preferential inhibitor) decreased NE-induced contractions of aortic rings from MS rats at all the ages, with meloxicam being the most potent. Acetylsalicylic acid also significantly reduced the maximum responses of ACh-induced vasorelaxation of aortic rings from MS rats, but indomethacin and meloxicam had no effect. NSAIDs can directly affect vascular responses in aging MS rats. Understanding the effects of NSAIDs on blood vessels may improve the treatment of cardiovascular diseases and MS in the elders.

Lipoxins, resolvins, protectins, maresins and nitrolipids, and their clinical implications with specific reference to cancer: part I

Obesity, insulin resistance, essential hypertension, Type 2 diabetes, nonalcoholic fatty liver disease, coronary heart disease, osteoporosis, renal failure, Alzheimer’s disease, depression, schizophrenia, aging, rheumatological conditions and cancer are low-grade systemic inflammatory conditions in which there is an increase in proinflammatory cytokines and reactive oxygen species, reactive nitrogen species, and proinflammatory eicosanoids, while a decrease in the cellular antioxidants, anti-inflammatory cytokines and certain polyunsaturated fatty acids, and their anti-inflammatory products such as lipoxins (LXs), resolvins (Rvs), protectins, maresins and nitrolipids occurs. This imbalance between the pro- and anti-inflammatory molecules in these diseases suggests that therapeutic strategies directed to suppress inappropriate inflammation may aid recovery from these diseases. It is proposed that both local and systemic delivery of LXs, Rvs, protectins, maresins and nitrolipids, and/or their more stable synthetic analogs, may prove to be useful in these diseases. In this part I of the review, the discussion is centered on the role of LXs, Rvs, protectins and nitrolipids in cancer.

Lipoxins, resolvins, protectins, maresins and nitrolipids, and their clinical implications with specific reference to diabetes mellitus and other diseases: part II

Obesity, insulin resistance, essential hypertension, Type 2 diabetes, nonalcoholic fatty liver disease, coronary heart disease, osteoporosis, renal failure, Alzheimer’s disease, depression, schizophrenia, aging and rheumatological conditions are low-grade systemic inflammatory conditions, in which there is an increase in the production of proinflammatory cytokines, reactive oxygen species, reactive nitrogen species and proinflammatory eicosanoids, while a decrease in the cellular antioxidants, anti-inflammatory cytokines and certain polyunsaturated fatty acids, and their anti-inflammatory products, lipoxins (LXs), resolvins (Rvs), protectins, maresins and nitrolipids, occurs. This imbalance between the pro- and anti-inflammatory molecules in these diseases suggests that therapeutic strategies directed to suppress inappropriate inflammation and enhance the synthesis/action of anti-inflammatory bioactive lipids may aid the prevention of and recovery from these diseases. It is proposed that both local and systemic delivery of LXs, Rvs, protectins, maresins and nitrolipids and/or their more stable synthetic analogs may prove to be useful in these diseases. In this part II of the review, the discussion is centered on the role of LXs, Rvs, protectins and nitrolipids in diabetes mellitus and other diseases.

A defect in the activities of Δ and Δ desaturases and pro-resolution bioactive lipids in the pathobiology of non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) is a low-grade systemic inflammatory condition, since liver and adipose tissue tumor necrosis factor-α (TNF-α) and TNF receptor 1 transcripts and serum TNF-α levels are increased and IL-6(-/-) mice are less prone to NAFLD. Fatty liver damage caused by high-fat diets is associated with the generation of pro-inflammatory prostaglandin E(2) (PGE(2)). A decrease in the levels of arachidonic acid (AA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and the usefulness of EPA and DHA both in the prevention and management of NAFLD has been reported. AA, EPA and DHA and their anti-inflammatory products lipoxins (LXs), resolvins and protectins suppress IL-6 and TNF-α and PGE(2) production. These results suggest that the activities of Δ(6) and Δ(5) desaturases are reduced in NAFLD and hence, the dietary essential fatty acids, linoleic acid (LA) and α-linolenic acid (ALA) are not metabolized to their long-chain products AA, EPA and DHA, the precursors of anti-inflammatory molecules, LXs, resolvins and protectins that could pre vent NAFLD. This suggests that an imbalance between pro- and anti-inflammatory bioactive lipids contribute to NAFLD. Hence, it is proposed that plasma and tissue levels of AA, EPA, DHA and LXs, resolvins and protectins could be used as predictors and prognostic biomarkers of NAFLD. It is suggested that the synthesis and use of more stable analogues of LXs, resolvins and protectins need to be explored in the prevention and management of NAFLD.

Vagus nerve stimulation as a strategy to prevent and manage metabolic syndrome

An increase in pro-inflammatory cytokines, decrease in endothelial nitric oxide (eNO) and adiponectin levels and an alteration in hypothalamic peptides and gastrointestinal hormones such as incretins and cholecystokinin that regulate satiety, hunger, and food intake occur in metabolic syndrome. Thus, metabolic syndrome is a low-grade systemic inflammatory condition and could be due to inappropriate cross-talk between the peripheral tissues and the hypothalamic centers implying that methods designed to restore these two abnormalities to normal could be of significant benefit in metabolic syndrome. Vagus nerve stimulation has been shown to suppress inflammation and acetylcholine, the principal vagal neurotransmitter, modulates the actions of several hypothalamic peptides and incretins and cholecystokinin. Based on these evidences, it is proposed that vagus nerve stimulation could be of significant benefit in the management of the metabolic syndrome.

Metabolic syndrome is a low-grade systemic inflammatory condition

An increase in proinflammatory cytokines, a decrease in endothelial nitric oxide and adiponectin levels and an alteration in hypothalamic peptides and gastrointestinal hormones that regulate satiety, hunger and food intake all occur in metabolic syndrome. Consumption of a diet that is energy dense and rich in saturated and trans-fats by pregnant women and lactating mothers, in childhood and adult life may trigger changes in the hypothalamic and gut peptides and hormones. Such changes modulate immune response and inflammation and lead to alterations in the hypothalamic ‘bodyweight/appetite/satiety set point’ and result in the initiation and development of the metabolic syndrome. Roux-en-gastric bypass induces weight loss, decreases the levels of cytokines and restores hypothalamic neuropeptides and gut hormones and the hypothalamic bodyweight/appetite/satiety set point to normal. Thus, metabolic syndrome is a low-grade systemic inflammatory condition with its origins in the perinatal period and childhood.

Lipoxins, Resolvins, Protectins, Maresins, and Nitrolipids: Connecting Lipids, Inflammation, and Cardiovascular Disease Risk

Essential fatty acids and their metabolites (γ-linolenic acid [GLA], dihomo-GLA, arachidonic acid, eicosapentaenoic acid, and docosahexaenoic acid; prostaglandin E1; prostacyclin [PGI2]; PGI3; lipoxins; resolvins; protectins; maresins; and nitrolipids) prevent platelet aggregation, produce vascular relaxation, inhibit neutrophil degranulation and superoxide formation, inhibit platelet activation, possess peroxisome proliferator-activated receptor-γ ligand activity, and release nitric oxide. Thus, they lower blood pressure, are anti-arrhythmic and anti-inflammatory in nature, reduce low-density lipoprotein cholesterol, ameliorate the adverse actions of homocysteine, activate telomerase, and have cytoprotective properties—actions that prevent atherosclerosis and cardiovascular disease. Because coronary heart disease (CHD) and atherosclerosis are low-grade systemic inflammatory conditions, it is likely that reduced formation of lipoxins, resolvins, protectins, maresins, and nitrolipids plays a significant role in the pathogenesis of CHD. Hence, development of stable synthetic analogues of lipoxins, resolvins, protectins, and maresins may form a new therapeutic approach to CHD and other low-grade systemic inflammatory conditions.

Osteoclastogenesis by Bone Marrow-Derived Macrophages Is Enhanced in Obese Mice

Obesity induces a low-grade systemic chronic inflammatory condition for which macrophages are responsible. We hypothesized that obesity affects osteoclastogenesis by acting on bone marrow-derived macrophages (BMM). Male mice were fed a high-fat diet (45% of energy) or a standard diet (10% of energy) for 13 wk. We found that the density of the femurs of obese mice was significantly lower than that of the femurs of lean mice. Osteoclastogenesis was enhanced in the BMM from obese mice. Lower levels of interleukin (IL)-10 were generated by the BMM from obese mice than by those from lean mice upon stimulation of receptor activator of nuclear factor-κB ligand. Neutralization of IL-10 in the BMM from obese mice was not as effective in increasing osteoclast (OC) formation as that in those from lean mice. Exogenous IL-10 inhibited OC formation more strongly in the BMM from obese mice than those from lean mice. The elevated level of OC formation in the BMM from obese mice may thus be due to in part to the lower level of IL-10, a negative regulator of osteoclastogenesis. Our results suggest that obesity is associated with bone loss via enhanced osteoclastogenesis due to reduced IL-10 production by the BMM from obese mice.

Transgenic fat-1 mouse as a model to study the pathophysiology of cardiovascular, neurological and psychiatric disorders.

Polyunsaturated fatty acids (PUFAs) form an important constituent of all the cell membranes in the body. PUFAs such as arachidonic acid (AA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) form precursors to both pro-inflammatory and anti-inflammatory compounds. Low-grade systemic inflammation occurs in clinical conditions such as insulin resistance, hypertension, type 2 diabetes mellitus, atherosclerosis, coronary heart disease, lupus, schizophrenia, Alzheimer's disease, and other dementias, cancer and non-alcoholic fatty liver disease (NAFLD) that are also characterized by an alteration in the metabolism of essential fatty acids in the form of excess production of pro-inflammatory eicosanoids and possibly, decreased synthesis and release of anti-inflammatory lipoxins, resolvins, protectins and maresins. We propose that low-grade systemic inflammation observed in these clinical conditions is due to an imbalance in the metabolism of essential fatty acids that is more in favour of pro-inflammatory molecules. In this context, transgenic fat-1 mouse that is designed to convert n-6 to n-3 fatty acids could form an ideal model to study the altered metabolism of essential fatty acids in the above mentioned conditions. It is envisaged that low-grade systemic inflammatory conditions are much less likely in the fat-1 mouse and/or these diseases will run a relatively mild course. Identifying the anti-inflammatory compounds from n-3 fatty acids that suppress low-grade systemic inflammatory conditions and understanding their mechanism(s) of action may lead to newer therapeutic strategies.

Gene and protein expression profiling of the fat-1 mouse brain

Polyunsaturated fatty acids (PUFAs) are essential structural components of all cell membranes and, more so, of the central nervous system. Several studies revealed that n-3 PUFAs possess anti-inflammatory actions and are useful in the treatment of dyslipidemia. These actions explain the beneficial actions of n-3 PUFAs in the management of cardiovascular diseases, inflammatory conditions, neuronal dysfunction, and cancer. But, the exact molecular targets of these beneficial actions of n-3 PUFAs are not known. Mice engineered to carry a fat-1 gene from Caenorhabditis elegans add a double bond into an unsaturated fatty acid hydrocarbon chain and convert n-6 to n-3 fatty acids. This results in an abundance of n-3 eicosapentaenoic acid and docosapentaenoic acid specifically in the brain and a reduction in n-6 fatty acids of these mice that can be used to evaluate the actions of n-3 PUFAs. Gene expression profile, RT-PCR and protein microarray studies in the hippocampus and whole brain of wild-type and fat-1 transgenic mice revealed that genes and proteins concerned with inflammation, apoptosis, neurotransmission, and neuronal growth and synapse formation are specifically modulated in fat-1 mice. These results may explain as to why n-3 PUFAs are of benefit in the prevention and treatment of diseases such as Alzheimer's disease, schizophrenia and other diseases associated with neuronal dysfunction, low-grade systemic inflammatory conditions, and bronchial asthma. Based on these data, it is evident that n-3 PUFAs act to modulate specific genes and formation of their protein products and thus, bring about their various beneficial actions.

Homocysteine Upregulates Resistin Production From Adipocytes In Vivo and In Vitro

Homocysteine (Hcy) is epidemiologically related to insulin resistance, which has been speculated to be a low-grade systemic inflammatory condition. Resistin acts as a critical mediator of insulin resistance associated with inflammatory conditions. We aimed to determine whether Hcy can induce insulin resistance by directly regulating the expression and secretion of resistin from adipose tissue. The effect of Hcy on the expression and secretion of resistin and insulin resistance was investigated using primary rat adipocytes and mice with hyperhomocysteinemia (HHcy). Hcy impaired glucose transport and, particularly, the insulin signaling pathway as shown by decreased insulin-stimulated tyrosine phosphorylation of insulin receptor and insulin receptor substrate (IRS)-1, increased serine phosphorylation of IRS-1, and inhibited Akt phosphorylation both in vitro and in vivo, and these impairments were accompanied by an increase in resistin expression. Compared with normal mice, HHcy mice with a clinically relevant level of plasma Hcy (19 micromol/l) showed significantly increased resistin production from adipose tissue (33.38 +/- 3.08 vs. 19.27 +/- 1.71 ng/ml, P < 0.01). Hcy (300-1000 micromol/l) also increased mRNA expression of resistin in primary rat adipocytes in a time- and concentration-dependent manner, with maximal induction at 24 h of approximately fourfold with 1,000 micromol/l. In addition, Hcy-induced resistin expression attenuated by treatment with reactive oxygen species (ROS) scavengers, protein kinase C (PKC), and nuclear factor (NF)-kappaB inhibitors implies a role in the process for ROS, PKC, and NF-kappaB. HHcy may promote insulin resistance through the induction of resistin expression and secretion from adipocytes via the activation of the ROS-PKC-NF-kappaB pathway.

Can essential fatty acids reduce the burden of disease(s)?

Coronary heart disease, stroke, diabetes mellitus, hypertension, cancer, depression schizophrenia, Alzheimer's disease, and collagen vascular diseases are low-grade systemic inflammatory conditions that are a severe burden on health care resources. Essential fatty acids (EFAs) and their metabolites: eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), gamma-linolenic acid (GLA), dihomo-gamma-linolenic acid (DGLA), and arachidonic acid (AA) and their products: prostaglandin E1, prostacyclin, lipoxins, resolvins, and protectins suppress inflammation, augment healing, and are of benefit in the prevention and management of these conditions. Hence, supplementation of EFAs could reduce burden of these disease(s).

Metabolic Syndrome X is a Low-Grade Systemic Inflammatory Condition with its Origins in the Perinatal Period

Metabolic Syndrome X is a Low-Grade Systemic Inflammatory Condition with its Origins in the Perinatal Period

Obesity and its relationship to coronary heart disease

There is reasonable evidence to believe that obesity and its associated conditions such as hypertension, dyslipidemia, type 2 diabetes mellitus, atherosclerosis, and coronary heart disease are low-grade systemic inflammatory conditions.1,2 Although adipose tissue distribution is dependent on genetic, environmental, and hormonal factors, there are distinct functional differences among adipose cells depending on their location. For instance, gluteal–femoral fat cells in females have a higher lipoprotein lipase (LPL) activity, higher insulin receptor binding, and higher rates of non-insulin-stimulated and maximally insulin-stimulated rates of glucose transport and glucose metabolism, whereas omental adipose tissue contains more number of glucocorticoid receptors (GR) compared with subcutaneous adipose tissue with similar Kd values, whereas LPL activity in subcutaneous adipose tissue is lower compared with omental adipose tissue. Leptin mRNA expression …