Changes in skeletal integrity and marrow adiposity during high-fat diet and after weight loss

The prevalence of obesity has continued to rise over the past three decades leading to significant increases in obesity-related medical care costs from metabolic and non-metabolic sequelae. It is now clear that expansion of body fat leads to an increase in inflammation with systemic effects on metabolism. In mouse models of diet-induced obesity there is also an expansion of bone marrow adipocytes. However, the persistence of these changes after weight-loss has not been well described. The objective of this study was to investigate the impact of high-fat diet (HFD) and subsequent weight-loss on skeletal parameters in C57Bl6/J mice. Male mice were given a normal chow diet (ND) or 60% HFD at 6-weeks of age for 12-, 16-, or 20-weeks. A third group of mice was put on HFD for 12-weeks and then on ND for 8-weeks to mimic weight-loss. After these dietary challenges the tibia and femur were removed and analyzed by microCT for bone morphology. Decalcification followed by osmium staining was used to assess bone marrow adiposity and mechanical testing was performed to assess bone strength. After 12-, 16-, or 20-weeks of HFD, mice had significant weight gain relative to controls. Body mass returned to normal after weight-loss. Marrow adipose tissue (MAT) volume in the tibia increased after 16-weeks of HFD and persisted in the 20-week HFD group. Weight loss prevented HFD-induced MAT expansion. Trabecular bone volume fraction, mineral content, and number were decreased after 12-, 16-, or 20-weeks of HFD, relative to ND controls, with only partial recovery after weight-loss. Mechanical testing demonstrated decreased fracture resistance after 20-weeks of HFD. Loss of mechanical integrity did not recover after weight-loss. Our study demonstrates that HFD causes long-term, persistent changes in bone quality, despite prevention of marrow adipose tissue accumulation, as demonstrated through changes in bone morphology and mechanical strength in a mouse model of diet-induced obesity and weight-loss

CD40 promotes MHC class II expression on adipose tissue macrophages and regulates adipose tissue CD4+ T cells with obesity

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/142158/1/jlb1107-sup-0002.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/142158/2/jlb1107-sup-0003.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/142158/3/jlb1107.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/142158/4/jlb1107-sup-0001.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/142158/5/jlb1107-sup-0004.pd

Frontline Science: Rapid adipose tissue expansion triggers unique proliferation and lipid accumulation profiles in adipose tissue macrophages

Obesityâ related changes in adipose tissue leukocytes, in particular adipose tissue macrophages (ATMs) and dendritic cells (ATDCs), are implicated in metabolic inflammation, insulin resistance, and altered regulation of adipocyte function. We evaluated stromal cell and white adipose tissue (WAT) expansion dynamics with high fat diet (HFD) feeding for 3â 56 days, quantifying ATMs, ATDCs, endothelial cells (ECs), and preadipocytes (PAs) in visceral epididymal WAT and subcutaneous inguinal WAT. To better understand mechanisms of the early response to obesity, we evaluated ATM proliferation and lipid accumulation. ATMs, ATDCs, and ECs increased with rapid WAT expansion, with ATMs derived primarily from a CCR2â independent resident population. WAT expansion stimulated proliferation in resident ATMs and ECs, but not CD11c+ ATMs or ATDCs. ATM proliferation was unperturbed in Csf2â and Rag1â deficient mice with WAT expansion. Additionally, ATM apoptosis decreased with WAT expansion, and proliferation and apoptosis reverted to baseline with weight loss. Adipocytes reached maximal hypertrophy at 28 days of HFD, coinciding with a plateau in resident ATM accumulation and the appearance of lipidâ laden CD11c+ ATMs in visceral epididymal WAT. ATM increases were proportional to tissue expansion and adipocyte hypertrophy, supporting adipocyteâ mediated regulation of resident ATMs. The appearance of lipidâ laden CD11c+ ATMs at peak adipocyte size supports a role in responding to ectopic lipid accumulation within adipose tissue. In contrast, ATDCs increase independently of proliferation and may be derived from circulating precursors. These changes precede and establish the setting in which largeâ scale adipose tissue infiltration of CD11c+ ATMs, inflammation, and adipose tissue dysfunction contributes to insulin resistance.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/142947/1/jlb10097_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/142947/2/jlb10097.pd

Weight Regain in Formerly Obese Mice Hastens Development of Hepatic Steatosis Due to Impaired Adipose Tissue Function

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/155467/1/oby22788-sup-0001-Supinfo.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/155467/2/oby22788_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/155467/3/oby22788.pd

Inflammatory responses to dietary and surgical weight loss in male and female mice

Abstract Background Weight loss by surgery or lifestyle changes is strongly recommended for obese individuals to improve metabolic health, but the underlying impairments that persist from a history of obesity remain unclear. Recent investigations demonstrate a persistent inflammatory state with weight loss and bariatric surgery, but the mechanism and impact are not fully understood. Additionally, these studies have not been performed in females although women are the majority of individuals undergoing weight loss interventions. Methods The goal of this study was to determine the sex differences in metabolically induced inflammation after dietary weight loss (WL) or bariatric surgery. Following a 60% high-fat diet (HFD) for 12 weeks, C57Bl/6j mice underwent either a dietary switch to normal chow for WL or vertical sleeve gastrectomy (VSG) and were evaluated 8 weeks after intervention. WL effects on myelopoiesis were further evaluated with bone marrow chimeras. Results Both sexes had a decrease in adiposity and total weight following WL or VSG intervention. With HFD, females had very little inflammation and no further increase with WL, but males had persistent inflammation even after WL despite metabolic improvement. Interestingly, after VSG, myeloid inflammation was increased in the livers of males and to a lesser extent in females. Conclusions These studies demonstrate that regardless of sex, it is critical to assess an individuals’ history of obesity rather than just rely on current weight status in medical decision-making. There are long-lasting effects on tissue inflammation in both sexes especially with surgical weight loss. Dietary change is overall most effective to improve meta-inflammation in obese males on its own or in combination with surgical weight loss.https://deepblue.lib.umich.edu/bitstream/2027.42/148527/1/13293_2019_Article_229.pd

The relationship between body fat mass percentiles and inflammation in children

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/106924/1/oby20710.pd

The relationship between adiposity and bone density in U.S. children and adolescents.

In adults, obesity has been associated with several health outcomes including increased bone density. Our objective was to evaluate the association between percent body fat and fat mass with bone mineral density (BMD) in a nationally representative population of children and adolescents.A total of 8,348 participants 8-18 years of age from the National Health and Nutrition Examination Survey (NHANES) 1999-2006 had whole body DXA scans performed. We conducted linear regressions to examine the relationship between percent body fat and fat mass with outcome variables of total body, pelvic and lumbar spine areal BMD (aBMD), controlling for lean body mass and assessing for gender and race/ethnicity interactions.We found evidence of gender and race/ethnicity interactions with percent body fat and total fat mass for the different BMD areas. Generally, there were decreases in total body aBMD (p<0.001) and lumbar spine aBMD (p<0.001) with increasing percent body fat and total fat mass, with less consistent patterns for pelvic aBMD.Our findings of regional differences in the relationship of adiposity to aBMD in children and adolescents with significant interactions by gender and race/ethnicity emphasizes the need for further investigations to understand the impact of adiposity on bone health outcomes