Exercise enhances insulin sensitivity; it also improves adipocyte metabolism and reduces adipose tissue inflammation through poorly-defined mechanisms. Fibroblast growth factor 21 (FGF21) is a pleiotropic hormone-like protein whose insulin-sensitizing properties are predominantly mediated via receptor signaling in adipose tissue (AT). Recently, FGF21 has also been demonstrated to have anti-inflammatory properties. Meanwhile, an association between exercise and increased circulating FGF21 levels has been reported in some, but not all studies. Thus, the role that FGF21 plays in mediating the positive metabolic effects of exercise in AT are unclear. In this study, FGF21 knock-out (KO) mice were used to directly assess the role of FGF21 in mediating the metabolic and anti-inflammatory effects of exercise on white AT (WAT) and brown AT (BAT). Male FGF21KO and wild-type mice were provided running wheels or remained sedentary for 8 weeks (n=9–15/group) and compared for adiposity, insulin sensitivity (i.e., HOMA-IR, Adipo-IR), and AT inflammation and metabolic function (e.g., mitochondrial enzyme activity, subunit content). Adiposity and Adipo-IR were increased in FGF21KO mice and decreased by EX. The BAT of FGF21KO animals had reduced mitochondrial content and decreased relative mass, both normalized by EX. WAT and BAT inflammation was elevated in FGF21KO mice, reduced in both genotypes by EX. EX increased WAT Pgc1alpha gene expression, citrate synthase activity, COX I content, and total AMPK content in WT but not FGF21KO mice. Collectively, these findings reveal a previously unappreciated anti-inflammatory role for FGF21 in WAT and BAT, but do not support that FGF21 is necessary for EX-mediated anti-inflammatory effects.

Carbohydrate ingestion and level of concentric versus eccentric muscle activity may alter exercise-induced health benefits for individuals who have high waist circumference as a metabolic risk factor. The purpose of this study was to determine whether metabolic and inflammation responses to an exercise recovery meal differ between women with lower (Lo-WC, <80 cm) compared with higher (Hi-WC) waist circumference when the exercise is primarily concentric (uphill walking; UPHILL) versus primarily eccentric (downhill walking; DOWNHILL). Recreationally active women (age, 18-39 years; body mass index, 19-35.4 m·kg; Lo-WC, n = 13; Hi-WC, n = 10) completed UPHILL, DOWNHILL, and resting (CONTROL) conditions followed 30 min later by a mixed meal tolerance test (MMTT) with carbohydrates to protein ratio of 4:1, and blood glucose, insulin, and inflammation markers were compared across conditions. Compared with Lo-WC, the Hi-WC group had higher (p < 0.05) (i) insulin during the MMTT in CONTROL (mean ± SE; 48.5 ± 8.2 vs 22.9 ± 2.8 pmol·L), (ii) baseline (0.7 ± 0.4 vs 2.0 ± 1.7 pg·mL) interleukin-6 (IL-6), and (iii) IL-6 responses 8 h after UPHILL and CONTROL. Both groups had (i) increases in IL-6 at 0 h after UPHILL and at 8 h after DOWNHILL, and (ii) lower glycemic responses in UPHILL. Women with Hi-WC had higher IL-6 at rest and delayed increases in IL-6 after a high-carbohydrate meal in all conditions. This is consistent with an inflammation response to the meal and or uphill walking exercise. However, both concentrically and eccentrically biased exercises offered benefits to insulin responses to a high carbohydrate meal for Hi-WC.

Objective The aim of this study was to examine the effects of sex and menopausal status on depot‐specific estrogen signaling in white adipose tissue (AT) in age‐matched men and women with morbid obesity. Methods A total of 28 premenopausal women, 16 postmenopausal women, and 27 age‐matched men undergoing bariatric surgery were compared for omental (OM) AT (OMAT) and abdominal subcutaneous (SQ) AT (SQAT) genes and proteins. Results With the exception of fasting nonesterified fatty acids being higher in women (P < 0.01), no differences were found in other indicators of glucose and lipid metabolism. In OMAT, estrogen receptor (ER) beta (ERβ) levels were higher in older women than in younger women and older men (sex‐age interaction, P < 0.01), and aromatase expression was higher in older men than in older women (P < 0.05). In SQAT, women had lower expression of ERβ than men (P < 0.05). Protein content of ER alpha and ERβ was highly correlated with the mitochondrial protein uncoupling protein 1 across sexes and ages (P < 0.001). Age increased SQ inflammatory gene expression in both sexes. Conclusions In morbid obesity, sex and age affect AT ERs, lipid metabolism, mitochondrial uncoupling protein 1, and inflammatory expression in an AT depot–dependent manner. The SQAT immunometabolic profile is heavily influenced by age and menopause status, more so than OMAT.

Increases in the prevalence of obesity and insulin resistance have paralleled lifestyle changes such as insufficient sleep.Approximately 33%-45% of American adults do not obtain the recommended 7-9 h of sleep/night, and about 40% of adults choose to sleep longer on weekends to "catch up" for the shorter weekday sleep schedules (Depner et al., 2019). Sleep restriction (SR) is strongly associated with systemic insulin resistance (Depner et al., 2019;Nedeltcheva, Kessler, Imperial, & Penev, 2009;Schmid et al., 2009), and therefore obese/overweight adults may be particularly susceptible to its adverse effects. Interestingly, 2 days of catch-up sleep have been shown to normalize insulin sensitivity in healthy men after 5 days of restricted sleep (Broussard,

During exercise, there is coordination between various hormonal systems to ensure glucoregulation. This study examined if hypoglycemia occurs during moderate-intensity exercise in non-obese and obese individuals with and without type 2 diabetes (T2D). Eighteen non-obese, 18 obese, and 10 obese with T2D completed 2 study days that included a meal at 1,800 h followed by rest (NOEX) or exercise (PMEX; 45 min/55% of VO 2 max 2 h post meal). Glucose, insulin, and glucagon concentrations were measured throughout this 5.5 h period. Subjects with T2D had elevated glucose responses to the meal on both study days, compared to non-obese and obese subjects ( P < 0.05). During evening exercise (PMEX), subjects with T2D had a greater drop in glucose concentration (−98.4 ± 13.3 mg/dL) compared to obese (−44.8 ± 7.1 mg/dL) and non-obese (−39.3 ± 6.1 mg/dL; P < 0.01) subjects. Glucose levels decreased more so in females than males in both conditions ( P < 0.01). Nadir glucose levels <70 mg/dL were observed in 33 subjects during NOEX and 39 subjects during PMEX. Obese males had a larger exercise-induced insulin drop than obese females ( P = 0.01). During PMEX, peak glucagon concentrations were elevated compared to NOEX ( P < 0.001). Male participants with T2D had an increased glucagon response during NOEX and PMEX compared to females ( P < 0.01). In conclusion, in individuals with varying glucose tolerance, there is a dramatic drop in glucose levels during moderate-intensity exercise, despite appropriate insulin concentrations prior to exercise, and glucagon levels rising during exercise. Moderate-intensity exercise can result in low glucose concentrations (<60 mg/dL), and yet many of these individuals will be asymptomatic.