Gavi et al. (1) investigated the association between visceral adipose tissue (VAT) mass by computed tomography and circulating retinol-binding protein-4 (RBP4) concentrations in nondiabetic subjects. They could not find a correlation between VAT and serum RBP4 concentrations, while VAT was inversely correlated with serum adiponectin concentrations in their subjects. The study by Gavi et al. did not support specific association between circulating …

https://care.diabetesjournals.org/content/diacare/30/3/e8.full.pdf

Plasma Retinol-Binding Protein-4 Concentrations Are Elevated in Human Subjects With Impaired Glucose Tolerance and Type 2 Diabetes: Response to Gavi et al.

Background and Purpose
The aims of this article are to review the effects of obesity on health and well-being and the evidence indicating they can be ameliorated by weight loss, and consider weight-management strategies that may help patients achieve and maintain weight loss.

Methods
Narrative review based on literature searches of PubMed up to May 2016 with no date limits imposed. Search included terms such as “obesity,” “overweight,” “weight loss,” “comorbidity,” “diabetes,” cardiovascular,” “cancer,” “depression,” “management,” and “intervention.”

Conclusions
Over one third of U.S. adults have obesity. Obesity is associated with a range of comorbidities, including diabetes, cardiovascular disease, obstructive sleep apnea, and cancer; however, modest weight loss in the 5%–10% range, and above, can significantly improve health-related outcomes. Many individuals struggle to maintain weight loss, although strategies such as realistic goal-setting and increased consultation frequency can greatly improve the success of weight-management programs. Nurse practitioners have key roles in establishing weight-loss targets, providing motivation and support, and implementing weight-loss programs.

Implications for Practice
With their in-depth understanding of the research in the field of obesity and weight management, nurse practitioners are well placed to effect meaningful changes in weight-management strategies deployed in clinical practice.

/pdf/obesity-risk-factors-complications-and-strategies-for-2h2caa4ff3.pdf

Obesity: Risk factors, complications, and strategies for sustainable long-term weight management

Importance Colorectal cancer (CRC) incidence and mortality among individuals younger than 50 years (early-onset CRC) are increasing. The reasons for such increases are largely unknown, although the increasing prevalence of obesity may be partially responsible. Objective To investigate prospectively the association between obesity and weight gain since early adulthood with the risk of early-onset CRC. Design, Setting, and Participants The Nurses’ Health Study II is a prospective, ongoing cohort study of US female nurses aged 25 to 42 years at study enrollment (1989). A total of 85 256 women free of cancer and inflammatory bowel disease at enrollment were included in this analysis, with follow-up through December 31, 2011. Validated anthropomorphic measures and lifestyle information were self-reported biennially. Statistical analysis was performed from June 12, 2017, to June 28, 2018. Exposures Current body mass index (BMI) (calculated as weight in kilograms divided by height in meters squared), BMI at 18 years of age, and weight gain since 18 years of age. Main Outcomes and Measures Relative risk (RR) for incident early-onset CRC. Results Among the 85 256 women studied, 114 cases of early-onset CRC were documented (median age at diagnosis, 45 years; interquartile range, 41-47 years) during 1 196 452 person-years of follow-up. Compared with women with a BMI of 18.5 to 22.9, the multivariable RR was 1.37 (95% CI, 0.81-2.30) for overweight women (BMI, 25.0-29.9) and 1.93 (95% CI, 1.15-3.25) for obese women (BMI, ≥30.0). The RR for each 5-unit increment in BMI was 1.20 (95% CI, 1.05-1.38;P = .01 for trend). Similar associations were observed among women without a family history of CRC and without lower endoscopy within the past 10 years. Both BMI at 18 years of age and weight gain since 18 years of age contributed to this observation. Compared with women with a BMI of 18.5 to 20.9 at 18 years of age, the RR of early-onset CRC was 1.32 (95% CI, 0.80-2.16) for women with a BMI of 21.0 to 22.9 and 1.63 (95% CI, 1.01-2.61) for women with a BMI of 23.0 or greater at 18 years of age (P = .66 for trend). Compared with women who had gained less than 5.0 kg or had lost weight, the RR of early-onset CRC was 1.65 (95% CI, 0.96-2.81) for women gaining 20.0 to 39.9 kg and 2.15 (95% CI, 1.01-4.55) for women gaining 40.0 kg or more (P = .007 for trend). Conclusions and Relevance Obesity was associated with an increased risk of early-onset CRC among women. Further investigations among men and to elucidate the underlying biological mechanisms are warranted.

/pdf/association-of-obesity-with-risk-of-early-onset-colorectal-3efillt1sw.pdf

Association of Obesity With Risk of Early-Onset Colorectal Cancer Among Women.

Adipose tissue in addition to its ability to keep lipids is now recognized as a real organ with both metabolic and endocrine functions. Recent studies demonstrated that in obese animals is established a status of adipocyte hypoxia and in this hypoxic state interaction between adipocytes and stromal vascular cells contribute to tumor development and progression. In several tumors such as breast, colon, liver and prostate, obesity represents a poor predictor of clinical outcomes. Dysfunctional adipose tissue in obesity releases a disturbed profile of adipokines with elevated levels of pro-inflammatory factors and a consequent alteration of key signaling mediators which may be an active local player in establishing the peritumoral environment promoting tumor growth and progression. Therefore, adipose tissue hypoxia might contribute to cancer risk in the obese population. To date the precise mechanisms behind this obesity-cancer link is not yet fully understood. In the light of information provided in this review that aims to identify the key mechanisms underlying the link between obesity and cancer we support that inflammatory state specific of obesity may be important in obesity-cancer link.

/pdf/obesity-and-cancer-the-role-of-adipose-tissue-and-adipo-1tf0ofp1bm.pdf

Obesity and cancer: the role of adipose tissue and adipo-cytokines-induced chronic inflammation

De novo lipogenesis (DNL) is a complex and highly regulated process in which carbohydrates from circulation are converted into fatty acids that are then used for synthesizing either triglycerides or other lipid molecules. Dysregulation of DNL contributes to human diseases such as obesity, type 2 diabetes, and cardiovascular diseases. Thus, the lipogenic pathway may provide a new therapeutic opportunity for combating various pathological conditions that are associated with dysregulated lipid metabolism. Hepatic DNL has been well documented, but lipogenesis in adipocytes and its contribution to energy homeostasis and insulin sensitivity are less studied. Recent reports have gained significant insights into the signaling pathways that regulate lipogenic transcription factors and the role of DNL in adipose tissues. In this review, we will update the current knowledge of DNL in white and brown adipose tissues with the focus on transcriptional, post-translational, and central regulation of DNL. We will also summarize the recent findings of adipocyte DNL as a source of some signaling molecules that critically regulate energy metabolism.

Regulation and Metabolic Significance of De Novo Lipogenesis in Adipose Tissues

Adipose tissue is a complex organ with endocrine, metabolic and immune regulatory roles. Adipose depots have been characterized to release several adipocytokines that work locally in an autocrine and paracrine fashion or peripherally in an endocrine fashion. Adipocyte hypertrophy and excessive adipose tissue accumulation, as occurs during obesity, dysregulates the microenvironment within adipose depots and systemically alters peripheral tissue metabolism. The term "adiposopathy" is used to describe this promotion of pathogenic adipocytes and associated adipose - elated disorders. Numerous epidemiological studies confirm an association between obesity and various cancer forms. Proposed mechanisms that link obesity/adiposity to high cancer risk and mortality include, but are not limited to, obesity-related insulin resistance, hyperinsulinemia, sustained hyperglycemia, glucose intolerance, oxidative stress, inflammation and/or adipocktokine production. Several epidemiological studies have demonstrated a relationship between specific circulating adipocytokines and cancer risk. The aim of this review is to define the function, in normal weight and obesity states, of well-characterized and novel adipokines including leptin, adiponectin, apelin, visfatin, resistin, chemerin, omentin, nesfatin and vaspin and summarize the data that relates their dysfunction, whether associated or direct effects, to specific cancer outcomes. Overall research suggests most adipokines promote cancer cell progression via enhancement of cell proliferation and migration, inflammation and anti-apoptosis pathways, which subsequently can prompt cancer metastasis. Further research and longitudinal studies are needed to define the specific independent and additive roles of adipokines in cancer progression and reoccurrence.

https://www.degruyter.com/downloadpdf/j/hmbci.2015.21.issue-1/hmbci-2014-0037/hmbci-2014-0037.xml

Adipose tissue, obesity and adipokines: role in cancer promotion

Adipose tissue is a complex endocrine organ with an intricate role in whole body homeostasis. Beyond storing energy, adipose tissue is fundamental in numerous processes including, but not limited to, metabolism, food intake and immune cell function. Adipokines and cytokines are the signaling factors from adipose tissue. These factors play a role in maintaining health, but are also candidates for pathologies associated with obesity. Indeed excessive adiposity causes dysregulation of these factors which negatively affect health and contribute to numerous obesity-induced co-morbidities. In particular, adipokines are fundamental in regulation of glucose homeostasis and insulin signaling, thus aberrant production of these adipose derived hormones correlates with the development and progression of type 2 diabetes. Therefore, elucidation of adipose regulation is crucial for understanding the pathophysiological basis of obesity and metabolic diseases such as type 2 diabetes. In the present review, we summarize current data on the relation between adipokines and adipose depot derived cytokines in the maintenance of glucose homeostasis. Specifically, physiological and molecular functions of several adipokines are defined with particular focus on interactions within the insulin-signaling pathway and subsequent regulation of glucose uptake in both standard and obesity-induced dysregulated conditions. This same relation will be discussed for cytokines and inflammation as well.

Adipose tissue: an endocrine organ playing a role in metabolic regulation.

The protective effects of lower body subcutaneous adiposity are linked to the depot functioning as a ”metabolic sink” receiving and sequestering excess lipid. This postulate, however, is based on i...

https://www.tandfonline.com/doi/pdf/10.1080/21623945.2018.1525252

Subcutaneous adipose tissue accumulation protects systemic glucose tolerance and muscle metabolism

Objectives
The spatial proximity of adipose depots to secondary lymph nodes allows a unique relation between the two systems. Obesity, predominately visceral adiposity, links to numerous diseases; hence, we postulate that secondary lymphatics within this region contributes to disease risk.

Material and methods
Male C57BL/6 mice were fed standard CHOW (18% kcal fat) or Western diet (45% kcal fat) for 7 weeks. Visceral and subcutaneous lymph nodes and associated adipose depots they occupy were excised. Lymph node morphology and resident immune cell populations were characterized via histopathology, immunofluorescence and flow cytometry. Adipose tissue immune cell populations were also characterized.

Results
Obesity caused lymph node expansion, increased viable cell number and deviations in immune cell populations. These alterations were exclusive to visceral lymph nodes. Notably, pro-inflammatory antigen presenting cells and regulatory T cells increased in number in the visceral lymph node. Obesity, however, reduced T regulatory cells in visceral lymph nodes. The visceral adipose depot also had greater reactivity towards HFD than subcutaneous, with a greater percent of macrophages, dendritic and CD8+ T cells. Immune cell number, in both the visceral and subcutaneous, however decreased as adipose depots enlarged.

Conclusion
Overall, HFD has a greater influence on visceral cavity than the subcutaneous. In the visceral lymph node, but not subcutaneous, HFD-induced obesity decreased cell populations that suppressed immune function while increasing those that regulate/activate immune response.

Josephine K. Fouts

Papers

Adipose tissue, obesity and adipokines: role in cancer promotion

Adipose tissue: an endocrine organ playing a role in metabolic regulation.

Subcutaneous adipose tissue accumulation protects systemic glucose tolerance and muscle metabolism

Diet-induced obesity causes visceral, but not subcutaneous, lymph node hyperplasia via increases in specific immune cell populations

Adipose tissue extrinsic factor: Obesity-induced inflammation and the role of the visceral lymph node.