Effects of Moderate and Subsequent Progressive Weight Loss on Metabolic Function and Adipose Tissue Biology in Humans with Obesity

“People with obesity and metabolic abnormalities often have concomitant systemic and adipose tissue ‘‘inflammation,’’ manifested by increased circulating inflammatory proteins and white blood cells, and increased subcutaneous adipose tissue macrophages, pro-inflammatory CD4 T-lymphocytes, and increased gene expression…”

“…inflammation, manifested by alterations in adipose tissue immune cell populations and increased gene expression of pro-inflammatory cytokines and chemokines, which cause systemic inflammation and insulin resistance (Berg and Scherer, 2005; Ferrante, 2007; Hotamisligil, 2006; Sun et al., 2013).”

“…including insulin resistance, b cell dysfunction, nonalcoholic fatty liver disease, dyslipidemia, and hypertension, which are important risk factors for the development of serious medical complications such as type 2 diabetes and coronary heart disease (Klein et al., 2002; Kopelman, 2000).”

“Although a mechanistic relationship between inflammation andmetabolic dysfunction has been demonstrated in rodent models (Berg and Scherer, 2005; Brestoff and Artis, 2015; Ferrante, 2007; Hotamisligil, 2006; Hotamisligil et al., 1995; Sun et al., 2013), the importance of low-grade inflammation in the pathogenesis of o…”

“…inflammation, manifested by alterations in adipose tissue immune cell populations and increased gene expression of pro-inflammatory cytokines and chemokines, which cause systemic inflammation and insulin resistance (Berg and Scherer, 2005; Ferrante, 2007; Hotamisligil, 2006; Sun et al., 2013).”

“Subjects with obesity had evidence of multi-organ insulin resistance (based on a homeostasis model assessment of insulin resistance score >2.0 [Levy et al., 1998] and results of a hyperinsulinemic-euglycemic clamp procedure conducted in conjunction with infusion of stable isotopically labeled…”

“Several large randomized controlled weight loss trials retrospectively evaluated the effects of different amounts of weight loss on clinical outcomes (Wing et al., 1987; Wing et al., 2011).”

“…with greater weight loss, e.g., after bariatric surgery-induced 20% weight loss that has been associated with decreased gene expression of pro-inflammatory cytokines and macrophage number in adipose tissue of people with obesity (Bradley et al., 2012; Cancello et al., 2005; Moschen et al., 2010).”

“To identify biological pathways that were significantly altered by weight loss, normalized data were subjected to PAGE as previously described (Fabbrini et al., 2015; Pearson et al., 2008; Yoshino et al., 2011).”

“, 2013), and production of ECM components (Halberg et al., 2009; Sun et al., 2013), can influence insulin sensitivity and whole-body glucose and”

“…weight loss needed to increase skeletal muscle insulin sensitivity has been unclear because of conflicting data from different studies reporting either no change or increased insulin-stimulated glucose uptake after 6%–8% weight loss (Kirk et al., 2009; Petersen et al., 2005; Petersen et al., 2012).”

“…ABCA1 (de Haan et al., 2014), regulators of cellular oxidative stress (Chutkow et al., 2010; Xue et al., 2013), and production of ECM components (Halberg et al., 2009; Sun et al., 2013), can influence insulin sensitivity and whole-body glucose and 6 Cell Metabolism 23, 1–11, April 12, 2016…”

“This biphasic adipose tissue immune response to weight loss observed in our subjects is consistent with the early increase and subsequent decrease in adipose tissue macrophage content observed after calorie restriction and weight loss in obese mice (Kosteli et al., 2010).”

“…that amoderate increase in adipose tissue inflammation during early weight loss provides a beneficial adaptive response to energy restriction, because adipose tissue inflammation could be required for appropriate adipose tissue remodeling (Rutkowski et al., 2015; Wernstedt Asterholm et al., 2014).”

“…that amoderate increase in adipose tissue inflammation during early weight loss provides a beneficial adaptive response to energy restriction, because adipose tissue inflammation could be required for appropriate adipose tissue remodeling (Rutkowski et al., 2015; Wernstedt Asterholm et al., 2014).”

“…assessment of overall b cell function is more informative than simply measuring the insulin secretory response alone because the insulin secretion rate and plasma insulin concentration needed to maintain normal glucose homeostasis depends on a person’s sensitivity to insulin (Bergman et al., 2002).”

“Although a mechanistic relationship between inflammation andmetabolic dysfunction has been demonstrated in rodent models (Berg and Scherer, 2005; Brestoff and Artis, 2015; Ferrante, 2007; Hotamisligil, 2006; Hotamisligil et al., 1995; Sun et al., 2013), the importance of low-grade inflammation in the pathogenesis of o…”

“Several large randomized controlled weight loss trials retrospectively evaluated the effects of different amounts of weight loss on clinical outcomes (Wing et al., 1987; Wing et al., 2011).”

“…weight loss needed to increase skeletal muscle insulin sensitivity has been unclear because of conflicting data from different studies reporting either no change or increased insulin-stimulated glucose uptake after 6%–8% weight loss (Kirk et al., 2009; Petersen et al., 2005; Petersen et al., 2012).”

“…clamp procedure conducted in conjunction with infusion of stable isotopically labeled tracers) and an increase in both systemic and adipose tissue markers of inflammation (compared with a group of lean adults that we studied previously) (Yoshino et al., 2012) (Table S1 and Figure S3).”

“People with obesity and metabolic abnormalities often have concomitant systemic and adipose tissue ‘‘inflammation,’’ manifested by increased circulating inflammatory proteins and white blood cells, and increased subcutaneous adipose tissue macrophages, pro-inflammatory CD4 T-lymphocytes, and increased gene expression…”

“…including insulin resistance, b cell dysfunction, nonalcoholic fatty liver disease, dyslipidemia, and hypertension, which are important risk factors for the development of serious medical complications such as type 2 diabetes and coronary heart disease (Klein et al., 2002; Kopelman, 2000).”

“…with greater weight loss, e.g., after bariatric surgery-induced 20% weight loss that has been associated with decreased gene expression of pro-inflammatory cytokines and macrophage number in adipose tissue of people with obesity (Bradley et al., 2012; Cancello et al., 2005; Moschen et al., 2010).”

“…with greater weight loss, e.g., after bariatric surgery-induced 20% weight loss that has been associated with decreased gene expression of pro-inflammatory cytokines and macrophage number in adipose tissue of people with obesity (Bradley et al., 2012; Cancello et al., 2005; Moschen et al., 2010).”

“Moreover, it was recently shown that increased adipose tissue markers of oxidative stress are associated with high-calorie diet-induced insulin resistance in people (Boden et al., 2015).”

“…because of conflicting results from different studies, reporting decreases, increases, and no changes in markers of inflammation after diet-induced weight loss (Capel et al., 2009; Clément et al., 2004; Dahlman et al., 2005; Johansson et al., 2012; Mali sová et al., 2014; Solá et al., 2009).”

“To identify biological pathways that were significantly altered by weight loss, normalized data were subjected to PAGE as previously described (Fabbrini et al., 2015; Pearson et al., 2008; Yoshino et al., 2011).”

“…in our subjects, namely the cholesterol transporter ABCA1 (de Haan et al., 2014), regulators of cellular oxidative stress (Chutkow et al., 2010; Xue et al., 2013), and production of ECM components (Halberg et al., 2009; Sun et al., 2013), can influence insulin sensitivity and whole-body…”

“…because of conflicting results from different studies, reporting decreases, increases, and no changes in markers of inflammation after diet-induced weight loss (Capel et al., 2009; Clément et al., 2004; Dahlman et al., 2005; Johansson et al., 2012; Mali sová et al., 2014; Solá et al., 2009).”

“…during high-dose insulin infusion (stage 2) of the clamp procedure. function is an important risk factor for future development of type 2 diabetes (Lorenzo et al., 2010), and an improvement in b cell function after weight loss induced by Roux-en-Y gastric bypass surgery is an important…”

“…diet-induced weight loss in our subjects, namely the cholesterol transporter ABCA1 (de Haan et al., 2014), regulators of cellular oxidative stress (Chutkow et al., 2010; Xue et al., 2013), and production of ECM components (Halberg et al., 2009; Sun et al., 2013), can influence insulin sensitivity…”

“…because of conflicting results from different studies, reporting decreases, increases, and no changes in markers of inflammation after diet-induced weight loss (Capel et al., 2009; Clément et al., 2004; Dahlman et al., 2005; Johansson et al., 2012; Mali sová et al., 2014; Solá et al., 2009).”

“…weight loss needed to increase skeletal muscle insulin sensitivity has been unclear because of conflicting data from different studies reporting either no change or increased insulin-stimulated glucose uptake after 6%–8% weight loss (Kirk et al., 2009; Petersen et al., 2005; Petersen et al., 2012).”

“…of many of the same metabolic pathways that were affected by diet-induced weight loss in our subjects, namely the cholesterol transporter ABCA1 (de Haan et al., 2014), regulators of cellular oxidative stress (Chutkow et al., 2010; Xue et al., 2013), and production of ECM components (Halberg et…”

“Gene expression was determined by using an ABI 7500 real-time PCR system (Invitrogen) and SYBRGreenMaster Mix (Invitrogen) as previously described (Fabbrini et al., 2015; Yoshino et al., 2014).”

“Fewer subjects would be needed to detect differences of similar magnitude within the same group (Magkos et al., 2011).”

“…because of conflicting results from different studies, reporting decreases, increases, and no changes in markers of inflammation after diet-induced weight loss (Capel et al., 2009; Clément et al., 2004; Dahlman et al., 2005; Johansson et al., 2012; Mali sová et al., 2014; Solá et al., 2009).”

“…risk factor for future development of type 2 diabetes (Lorenzo et al., 2010), and an improvement in b cell function after weight loss induced by Roux-en-Y gastric bypass surgery is an important determinant of which patients will achieve diabetes remission (Khanna et al., 2015; Lund et al., 2015).”

“…risk factor for future development of type 2 diabetes (Lorenzo et al., 2010), and an improvement in b cell function after weight loss induced by Roux-en-Y gastric bypass surgery is an important determinant of which patients will achieve diabetes remission (Khanna et al., 2015; Lund et al., 2015).”

“, prediabetes, hypertension, and obstructive sleep apnea).(1,20,21,27) In the semaglutide group, approximately 70% of participants achieved a weight loss of at least 10%, and approximately 50% achieved a weight loss of at least 15%.”