Excess adipose tissue is a hallmark of an overweight and/or obese state as well as a primary risk factor for breast cancer development and progression. In an overweight/obese state adipose tissue becomes dysfunctional due to rapid hypertrophy, hyperplasia, and immune cell infiltration which is associated with sustained low-grade inflammation originating from dysfunctional adipokine synthesis. Evidence also supports the role of excess adipose tissue (overweight/obesity) as a casual factor for the development of chemotherapeutic drug resistance. Obesity-mediated effects/modifications may contribute to chemotherapeutic drug resistance by altering drug pharmacokinetics, inducing chronic inflammation, as well as altering tumor-associated adipocyte adipokine secretion. Adipocytes in the breast tumor microenvironment enhance breast tumor cell survival and decrease the efficacy of chemotherapeutic agents, resulting in chemotherapeutic resistance. A well-know chemotherapeutic agent, doxorubicin, has shown to negatively impact adipose tissue homeostasis, affecting adipose tissue/adipocyte functionality and storage. Here, it is implied that doxorubicin disrupts adipose tissue homeostasis affecting the functionality of adipose tissue/adipocytes. Although evidence on the effects of doxorubicin on adipose tissue/adipocytes under obesogenic conditions are lacking, this narrative review explores the potential role of obesity in breast cancer progression and treatment resistance with inflammation as an underlying mechanism.

Breast cancer cells modulate lipid and fatty acid metabolism to sustain proliferation. The role of adipocytes in cancer treatment efficacy remains, however, to be fully elucidated. We investigated whether diet-induced obesity (DIO) affects the efficacy of doxorubicin treatment in a breast tumor-bearing mouse model. Female C57BL6 mice were fed a high fat or low fat diet for the full duration of the study (12 weeks). After 8 weeks, mice were inoculated with E0771 triple-negative breast cancer cells in the fourth mammary gland to develop breast tumor allographs. Tumor-bearing mice received either vehicle (Hank's balanced salt solution) or doxorubicin (chemotherapy). Plasma inflammatory markers, tumor, and mammary adipose tissue fatty acid composition, as well as protein expression of lipid metabolism markers were determined. The high fat diet (HFD) attenuated the treatment efficacy of doxorubicin. Both leptin and resistin concentrations were significantly increased in the HFD group treated with doxorubicin. Suppressed lipogenesis (decreased stearoyl CoA-desaturase-1) and lipolysis (decreased hormone-sensitive lipase) were observed in mammary adipose tissue of the DIO animals, whereas increased expression was observed in the tumor tissue of doxorubicin treated HFD mice. Obesogenic conditions induced altered tissue fatty acid (FA) compositions, which reduced doxorubicin's treatment efficacy. In mammary adipose tissue breast cancer cells suppressed the storage of FAs, thereby increasing the availability of free FAs and favored inflammation under obesogenic conditions.

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BackgroundSufficient evidence associate body shape to detrimental lifestyle diseases including the metabolic syndrome (MetS). The prevalence of the MetS, as well as effects of the MetS and body shape on body composition, insulin-like growth factor-1 (IGF-1), C-reactive protein (CRP) and sex hormone parameters were investigated in a female farm worker population in the Western Cape.MethodsWomen between the ages of 20–60 years were classified according to the International Diabetes Federation’s definition of the MetS. Assessments included body shape (android/gynoid), blood pressure, anthropometric, bioelectrical impedance analyses and blood analyses for fasting glucose and insulin, lipid profile, IGF-1, CRP, and sex hormone parameters.ResultsThe prevalence of the MetS was 52%, with abdominal obesity 68.8%, hypertension 66.4% and low high density lipoprotein-cholesterol (HDL-c) levels (64.1%) being the more prevalent MetS risk factors. The MetS, irrespective of body shape, was found to be associated with body mass index (p < 0.01), fat mass (%) (p < 0.01), waist circumference (p < 0.001), HDL-c (p < 0.001), systolic blood pressure (p < 0.05) and diastolic blood pressure (p < 0.01). No significant differences were observed for IGF-1, CRP and sex hormone parameters.ConclusionThe prevalence of the MetS and its individual risk factors were found to be significantly high in this female farm worker population. Additionally, the study showed that the MetS, body shape and/or both could predict differences in body composition, physiological and biochemical parameters in women.

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Background: Cardiovascular diseases (CVD) remains a primary cause of (central) obesity-associated mortality among African populations. Measures of adiposity are reported as prevalence’s in a South African (SA) female farm working population at risk for cardio-and metabolic disease related to body mass index, (BMI), waist-to-hip ratio (W:H), waist circumference (WC) and visceral adiposity index (VAI), biochemical and metabolic blood parameters.Methods: A cross-section of female farm workers (n=120) from the Boland region in SA between the ages 20-60 years were recruited and classified according to different anthropometric indices including BMI, W:H, WC and the VAI, and subsequently divided into normal- and at risk groups for each index. Blood samples were analysed for inflammatory markers, serum insulin, glucose and a full lipid profile.Results: Prevalence’s and significant differences for the different adiposity measures between normal and overweight groups were: (BMI: 25.8% - 74.2%; p<0.0001); (W:H: 57.5% - 42.5%; p<0.0001); (WC: 42.0% vs 58.3%; p<0.0001); and (VAI: 48.3% vs 51.7%; p<0.0001). Systolic blood pressure (p<0.01) and diastolic blood pressure (p=0.03) were different within the BMI grouping, as well as VAT% (p<0.001) and SAT% (p<0.01). Differences were reported for body mass, BMI, WC and VAI within the W:H and WC groupings. Systolic (p=0.04) and diastolic blood pressure (p=0.0009) were different in the WC grouping. Metabolic healthy and unhealthy women showed differences in BMI (p<0.05); W:H (p<0.0001); WC (p<0.0001). Systolic and diastolic blood pressure were different between metabolic healthy (p<0.05) and unhealthy women (p=0.0005). The inflammatory cytokines were similarly elevated in the normal and obese groups TNFα; (p<0.0001); IL-6; (p<0.01), MCP-1; (p=0.0001), and resistin; (p<0.0001). For the W:H, IL-6 (p<0.01) and blood glucose (p=0.006) were different. The WC grouping showed differences in resistin (p<0.0001), MCP-1 (p<0.0001, blood glucose (p<0.01, and insulin (p=0.0002). For metabolic healthy vs unhealthy women, resistin (p<0.0001); MCP-1 (p=0.0007); blood glucose (p<0.01) and insulin (p<0.05) were different.Conclusion: Women suffering from obesity showed a higher pro-inflammatory profile and higher risk for cardio-metabolic disease using the BMI as a measure of adiposity compared to WC, W:H and VAI.