Table 4.

Ten Takeaway Messages: Adiposopathy and Cancer. A 4-part series of articles published in a special issue of Hormone Molecular Biology and Clinical Investigation examined the role of adiposopathy and cancer.

1.	Cancer and (cardio) metabolic diseases are the two major ‘socio-epidemic’ illnesses in terms of prevalence and morbidity/mortality in Western industrial countries and developing countries. A major contributor to both are the multiple biological disturbances associated with adipose tissue dysfunction (i.e., adiposopathy) [57].
2.	Fat tissue is a paramount coordinator of key biological processes such as differentiation, tissue regeneration, cell growth, apoptosis, reproduction, immunity, inflammation, angiogenesis, metabolism, and thermoregulation. Adipose tissue dysfunction can lead or contribute to multiple pathologies such as obesity, type 2 diabetes mellitus, dyslipidemia, hypertension, atherosclerosis, metabolic syndrome, cognitive alteration, and/or cancer [56].
3.	Expansion of adipose tissue is achieved when proliferation and differentiation of new fat cells exceed fat cell death (apoptosis). Beyond storing excess energy, expansion of adipose tissue functions to sequester cytotoxic free fatty acids and lipid metabolites. Limitations in the proliferation and differentiation of peripheral subcutaneous adipose tissue and increase in fat deposition in the intraperitoneal area (visceral fat) promotes metabolic and vascular disturbances [58] that reflect a more carcinogenic clinical profile.
4.	Proposed mechanisms that link obesity/adiposity to high cancer risk and mortality include obesity-related insulin resistance, hyperinsulinemia, sustained hyperglycemia, glucose intolerance, oxidative stress, inflammation and/or adipocytokine production [59].
5.	In addition to increased release of pro-inflammatory factors, obesity is associated with a decrease in anti-inflammatory factors, such as a reduction in adiponectin. Adiponectin is a multimeric protein of the white adipose tissue presenting anti-inflammatory, insulin-sensitizing, anti-atherogenic, cardioprotective, and anti-neoplastic properties. Its anti-neoplastic actions are manifested via two mechanisms: (i) direct action on tumor cells by enhancing receptor-mediated signaling pathways and (ii) indirect action by regulating inflammatory responses, influencing cancer angiogenesis, and modulating insulin sensitivity at the target tissue site [60].
6.	Beyond the systemic tumor-promoting impact of adiposopathy (“sick fat”), local adipose tissue paracrine functions may lead to phenotypic and/or functional modifications of both adipocytes and cancer cells, as well as alterations in the extracellular matrix. In addition to de-differentiation processes, adiposopathy promotes cancer cell aggressiveness through promoting cancer proliferation, migration, and invasion, accompanied by tissue remodeling. In total, obesity allows for a locally permissive environment for cancer cells [61].
7.	Obesity is an important risk factor for several cancer types, such as colorectal, hepatic, esophageal, kidney, post-menopausal breast, and endometrial. Obesity or adiposopathy is also a poor prognostic factor for relapse-free survival and chemotherapy resistance [62].
8.	Breast cancer was one of the first cancer types where a positive correlation was found between obesity and breast cancer incidence and prognosis in post-menopausal women. Research supports that “sick” adipose tissue (adiposopathy) paracrine and endocrine functions play a role of adipose tissue in breast cancer initiation and progression – and may serve as an “ally of the enemy” and “collaborator” in human breast cancer [63].
9.	The adiposopathic hormone secretions most relevant to colorectal tumorigenesis include adiponectin, leptin, resistin, and ghrelin, which are involved in cell growth and proliferation, as well as tumor angiogenesis. Adiposopathy may facilitate an unfavorable adipokine profile, with an increase in pro-inflammatory and pro-cancerous immune response and a decrease in anti-inflammatory and anti-cancerous activity, potentially worsening colorectal cancer prognosis [64].
10.	Epidemiological studies demonstrate that racial and ethnic populations (e.g., non-Caucasian females, African-American females) with higher rates of obesity have higher mortality from endocrine-responsive cancers [62].