Obesity and Pancreatic Cancer: Insight into Mechanisms

The prevalence of obesity in adults and children has dramatically increased over the past decades. Obesity has been declared a chronic progressive disease and is a risk factor for a number of metabolic, inflammatory, and neoplastic diseases. There is clear epidemiologic and preclinical evidence that obesity is a risk factor for pancreatic cancer. Among various potential mechanisms linking obesity with pancreatic cancer, the adipose tissue and obesity-associated adipose tissue inflammation play a central role. The current review discusses selected topics and mechanisms that attracted recent interest and that may underlie the promoting effects of obesity in pancreatic cancer. These topics include the impact of obesity on KRAS activity, the role of visceral adipose tissue, intrapancreatic fat, adipose tissue inflammation, and adipokines on pancreatic cancer development. Current research on lipocalin-2, fibroblast growth factor 21, and Wnt5a is discussed. Furthermore, the significance of obesity-associated insulin resistance with hyperinsulinemia and obesity-induced gut dysbiosis with metabolic endotoxemia is reviewed. Given the central role that is occupied by the adipose tissue in obesity-promoted pancreatic cancer development, preventive and interceptive strategies should be aimed at attenuating obesity-associated adipose tissue inflammation and/or at targeting specific molecules that mechanistically link adipose tissue with pancreatic cancer in obese patients.

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Adipokines levels in HIV infected patients: lipocalin-2 and fatty acid binding protein-4 as possible markers of HIV and antiretroviral therapy-related adipose tissue inflammation

BMC Infectious Diseases ◽

10.1186/s12879-017-2925-4 ◽

2018 ◽

Vol 18 (1) ◽

Cited By ~ 5

Author(s):

Mario Luca Morieri ◽

Viola Guardigni ◽

Juana Maria Sanz ◽

Edoardo Dalla Nora ◽

Cecilia Soavi ◽

...

Keyword(s):

Adipose Tissue ◽

Fatty Acid ◽

Antiretroviral Therapy ◽

Fatty Acid Binding Protein ◽

Binding Protein ◽

Adipose Tissue Inflammation ◽

Lipocalin 2 ◽

Fatty Acid Binding ◽

Tissue Inflammation ◽

Acid Binding Protein

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Pro-inflammatory effects of DEHP in SGBS-derived adipocytes and THP-1 macrophages

Scientific Reports ◽

10.1038/s41598-021-85119-3 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Kristina Schaedlich ◽

Laura-Sophie Beier ◽

Judith Kolbe ◽

Martin Wabitsch ◽

Jana Ernst

Keyword(s):

Adipose Tissue ◽

Energy Homeostasis ◽

Overweight And Obesity ◽

Environmental Chemicals ◽

Low Grade ◽

Adipose Tissue Inflammation ◽

Tissue Inflammation ◽

Secreted Factors ◽

The Impact ◽

Dehp Exposure

AbstractIn the member countries of the Organization for Economic Co-operation and Development (OECD), overweight and obesity affect the majority of the population. The use of environmental chemicals, such as the plasticizer DEHP, has largely increased simultaneously with this development. DEHP is an "obesogen" that interferes with normal adipocyte differentiation and energy homeostasis. Obesity in turn is accompanied by chronic low-grade adipose tissue inflammation, leading to metabolic disorders such as type II diabetes. The main actors in adipose tissue inflammation are adipocytes and macrophages. However, the impact of DEHP on adipose tissue inflammation and the crosstalk between adipocytes and macrophages are unknown and the subjects of the current study. The influence of DEHP on inflammation was investigated in human Simpson–Golabi–Behmel syndrome (SGBS)-derived adipocytes and human THP-1 macrophages. The proinflammatory markers IL8, MCP1, IL1β, TNFα and others were measured (qRT-PCR, ELISA) in SGBS-derived adipocytes treated with DEHP [day 0 (d0)–d4; 50 µg/ml] and THP-1 macrophages cultured with conditioned medium (CM) from DEHP-treated adipocytes (SGBS-CM) (from d4 and d8). DEHP exposure led to a proinflammatory state in SGBS-derived adipocytes (e.g., increased secretion of IL8 and MCP1). Surprisingly, exposure of THP-1 macrophages to SGBS-CM did not show DEHP-induced effects. However, we demonstrated that medium containing (pre)adipocyte-secreted factors had a significant impact on the expression and secretion of macrophage and inflammatory markers in THP-1 macrophages in general and led to the significantly increased accumulation of intracellular lipid droplets.

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Flavonoids in adipose tissue inflammation and atherosclerosis: one arrow, two targets

Clinical Science ◽

10.1042/cs20200356 ◽

2020 ◽

Vol 134 (12) ◽

pp. 1403-1432 ◽

Cited By ~ 2

Author(s):

Manal Muin Fardoun ◽

Dina Maaliki ◽

Nabil Halabi ◽

Rabah Iratni ◽

Alessandra Bitto ◽

...

Keyword(s):

Adipose Tissue ◽

Fruits And Vegetables ◽

Metabolic Diseases ◽

Therapeutic Agents ◽

Adipose Tissue Inflammation ◽

Cellular Mechanisms ◽

Tissue Inflammation ◽

Cholesterol Levels ◽

Naturally Occurring ◽

Pro Inflammatory Cytokines

Abstract Flavonoids are polyphenolic compounds naturally occurring in fruits and vegetables, in addition to beverages such as tea and coffee. Flavonoids are emerging as potent therapeutic agents for cardiovascular as well as metabolic diseases. Several studies corroborated an inverse relationship between flavonoid consumption and cardiovascular disease (CVD) or adipose tissue inflammation (ATI). Flavonoids exert their anti-atherogenic effects by increasing nitric oxide (NO), reducing reactive oxygen species (ROS), and decreasing pro-inflammatory cytokines. In addition, flavonoids alleviate ATI by decreasing triglyceride and cholesterol levels, as well as by attenuating inflammatory mediators. Furthermore, flavonoids inhibit synthesis of fatty acids and promote their oxidation. In this review, we discuss the effect of the main classes of flavonoids, namely flavones, flavonols, flavanols, flavanones, anthocyanins, and isoflavones, on atherosclerosis and ATI. In addition, we dissect the underlying molecular and cellular mechanisms of action for these flavonoids. We conclude by supporting the potential benefit for flavonoids in the management or treatment of CVD; yet, we call for more robust clinical studies for safety and pharmacokinetic values.

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