How does adipose tissue fat content change after a weight loss intervention?

Abstract Abstract 3570 Background: Obesity increases the mortality of numerous types of cancer. Furthermore, children over 10 years of age who are obese at diagnosis of acute lymphoblastic leukemia (ALL) have twice the risk of relapse. We have found that obese mice transplanted with leukemia are more likely to relapse after treatment with chemotherapy. We further found that adipose tissue can protect ALL cells from chemotherapy in culture. But it is unclear whether a weight loss intervention after leukemia diagnosis will improve outcome. Hypothesis: A weight loss intervention by dietary modification in diet induced obese mice will decrease the ability of their adipose tissue explants to protect ALL cells from chemotherapy. Methods: Diet-induced obese C57Bl/6 mice (n=7) were switched to a low-fat diet either 3 or 21 days prior to sacrifice at 20 weeks of age. Adipose tissue explants (100 ± 5 mg) from perirenal, visceral, and subcutaneous sites were collected and used in transwell co-cultures with 250 X103 8093 murine pre-B ALL cells. Explants from non-dieted obese mice and lean mice were used as controls. Viable ALL cells were quantified using trypan blue exclusion after a 3-day exposure to 15 nM daunorubicin or 5 nM of vincristine. Results: Dietary intervention significantly reduced body weights in the short (39.2 ± 2.4 grams; P= 0.014) and long (32 ± 2.9 grams; P=0.041) diet groups compared to obese mice (44.5 grams ± 2.6). Leukemia cells were partially protected from daunorubicin by both visceral (21.5±15.7×103 viable cells, p=0.01) and perirenal (28.0±20.7×103, p=0.013) fat explants from obese mice, compared to cultures without adipose tissue (9.4±8.6×103). Fat explants from mice dieted for 3 days prior to collection showed similar protection of ALL cells from daunorubicin (not shown); however, fat explants from mice dieted for 21 days did not protect ALL cells from daunorubicin (visceral: 9.4±8.0×103, p=0.009; perirenal: 7.8±6.3×103, p=0.066 vs. obese). Similar findings were obtained with vincristine. Leukemia cells were protected from vincristine significantly by visceral fat from obese mice (50.8±5.9×103, p=0.01) and marginally by perirenal and subcutaneous fat (93.8±139.1×103, p=0.06 and 113.4±143.7×103, p=0.07 respectively) compared to cultures without adipose tissue (12.4±11.7×103). While short dieting did not restore sensitivity to vincristine, long dieting of obese mice reduced explants leukemia protection to vincristine significantly in visceral (21.8±20.2×103, p=0.004) and marginally in perirenal (34.9±43.3×103, p=0.06) explants compared to the obese group. Conclusions: Dietary intervention and weight loss in diet induced obese mice decreases the ability of adipose tissue ex vivo to protect ALL cells from daunorubicin and vincristine. These results could support a potential role for dietary intervention in improving leukemia outcome in obese patients. Disclosures: No relevant conflicts of interest to declare.

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Associations between breast adipose tissue, body fat distribution and cardiometabolic risk in women: cross-sectional data and weight-loss intervention

European Journal of Clinical Nutrition ◽

10.1038/ejcn.2011.35 ◽

2011 ◽

Vol 65 (7) ◽

pp. 784-790 ◽

Cited By ~ 18

Author(s):

B Schautz ◽

W Later ◽

M Heller ◽

M J Müller ◽

A Bosy-Westphal

Keyword(s):

Weight Loss ◽

Adipose Tissue ◽

Body Fat ◽

Cardiometabolic Risk ◽

Fat Distribution ◽

Body Fat Distribution ◽

Weight Loss Intervention ◽

Cross Sectional ◽

Breast Adipose Tissue ◽

Breast Adipose

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Abstract 2425: Moderate to vigorous physical activity reduces visceral adipose tissue in obese breast cancer survivors undergoing a weight loss intervention

10.1158/1538-7445.am2019-2425 ◽

2019 ◽

Author(s):

Carol J. Fabian ◽

Jennifer R. Klemp ◽

Jeffrey M. Burns ◽

Eric D. Vidoni ◽

Lauren Nye ◽

...

Keyword(s):

Breast Cancer ◽

Physical Activity ◽

Weight Loss ◽

Adipose Tissue ◽

Cancer Survivors ◽

Visceral Adipose Tissue ◽

Breast Cancer Survivors ◽

Vigorous Physical Activity ◽

Weight Loss Intervention ◽

Visceral Adipose

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Obesity-related elevations in plasma leucine are associated with alterations in enzymes involved in branched-chain amino acid metabolism

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00134.2007 ◽

2007 ◽

Vol 293 (6) ◽

pp. E1552-E1563 ◽

Cited By ~ 265

Author(s):

Pengxiang She ◽

Cynthia Van Horn ◽

Tanya Reid ◽

Susan M. Hutson ◽

Robert N. Cooney ◽

...

Keyword(s):

Weight Loss ◽

Adipose Tissue ◽

Amino Acid ◽

Human Subjects ◽

Subcutaneous Fat ◽

Zucker Rats ◽

Weight Loss Intervention ◽

Surgical Weight Loss ◽

Branched Chain Amino Acid ◽

Branched Chain

Elevations in branched-chain amino acids (BCAAs) in human obesity were first reported in the 1960s. Such reports are of interest because of the emerging role of BCAAs as potential regulators of satiety, leptin, glucose, cell signaling, adiposity, and body weight (mTOR and PKC). To explore loss of catabolic capacity as a potential contributor to the obesity-related rises in BCAAs, we assessed the first two enzymatic steps, catalyzed by mitochondrial branched chain amino acid aminotransferase (BCATm) or the branched chain α-keto acid dehydrogenase (BCKD E1α subunit) complex, in two rodent models of obesity ( ob/ob mice and Zucker rats) and after surgical weight loss intervention in humans. Obese rodents exhibited hyperaminoacidemia including BCAAs. Whereas no obesity-related changes were observed in rodent skeletal muscle BCATm, pS293, or total BCKD E1α or BCKD kinase, in liver BCKD E1α was either unaltered or diminished by obesity, and pS293 (associated with the inactive state of BCKD) increased, along with BCKD kinase. In epididymal fat, obesity-related declines were observed in BCATm and BCKD E1α. Plasma BCAAs were diminished by an overnight fast coinciding with dissipation of the changes in adipose tissue but not in liver. BCAAs also were reduced by surgical weight loss intervention (Roux-en-Y gastric bypass) in human subjects studied longitudinally. These changes coincided with increased BCATm and BCKD E1α in omental and subcutaneous fat. Our results are consistent with the idea that tissue-specific alterations in BCAA metabolism, in liver and adipose tissue but not in muscle, may contribute to the rise in plasma BCAAs in obesity.

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Abstract 2425: Moderate to vigorous physical activity reduces visceral adipose tissue in obese breast cancer survivors undergoing a weight loss intervention

10.1158/1538-7445.sabcs18-2425 ◽

2019 ◽

Author(s):

Carol J. Fabian ◽

Jennifer R. Klemp ◽

Jeffrey M. Burns ◽

Eric D. Vidoni ◽

Lauren Nye ◽

...

Keyword(s):

Breast Cancer ◽

Physical Activity ◽

Weight Loss ◽

Adipose Tissue ◽

Cancer Survivors ◽

Visceral Adipose Tissue ◽

Breast Cancer Survivors ◽

Vigorous Physical Activity ◽

Weight Loss Intervention ◽

Visceral Adipose

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Expression of macrophage genes within skeletal muscle correlates inversely with adiposity and insulin resistance in humans

Applied Physiology Nutrition and Metabolism ◽

10.1139/apnm-2017-0228 ◽

2018 ◽

Vol 43 (2) ◽

pp. 187-193 ◽

Cited By ~ 4

Author(s):

Dongmei Liu ◽

Flor Elisa Morales ◽

Heidi. B. IglayReger ◽

Mary K. Treutelaar ◽

Amy E. Rothberg ◽

...

Keyword(s):

Gene Expression ◽

Insulin Resistance ◽

Skeletal Muscle ◽

Weight Loss ◽

Adipose Tissue ◽

Insulin Sensitivity ◽

Muscle Tissue ◽

Skeletal Muscle Tissue ◽

Obese Patients ◽

Weight Loss Intervention

Local inflammation in obese adipose tissue has been shown to contribute to insulin resistance; however, the role of macrophage infiltration within skeletal muscle is still debatable. This study aimed to evaluate the association of skeletal muscle macrophage gene expression with adiposity levels and insulin sensitivity in obese patients. Twenty-two nondiabetic obese patients and 23 healthy lean controls were included. Obese patients underwent a 3-month weight loss intervention. Macrophage gene expression in skeletal muscle (quantitative real-time polymerase chain reaction), body composition (dual-energy X-ray absorptiometry), and insulin sensitivity (homeostatic model assessment (HOMA) and oral glucose tolerance test) were compared between groups and their associations were analyzed. To validate skeletal muscle findings, we repeated the analyses with macrophage gene expression in adipose tissue. Expression levels of macrophage genes (CD68, CD11b, CD206, CD16, CD40, and CD163) were lower in skeletal muscle tissue of obese versus lean participants. Macrophage gene expression was also found to be inversely associated with adiposity, fasting insulin, and HOMA (r = −0.4 ∼ −0.6, p < 0.05), as well as positively associated with insulin sensitivity (r = 0.4 ∼ 0.8, p < 0.05). On the other hand, adipose tissue macrophage gene expression showed higher levels in obese versus lean participants, presenting a positive association with adiposity levels. Macrophage gene expression, in both skeletal and adipose tissue samples, was only minimally affected by the weight loss intervention. In contrast with the established positive relationship between adiposity and macrophage gene expression, an unexpected inverse correlation between these 2 variables was observed in skeletal muscle tissue. Additionally, muscle macrophage gene expression was inversely correlated with insulin resistance.

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