The Effect of a Healthy Lifestyle on Future Physical Functioning in Midlife Women.

PURPOSE: This study aimed to examine the prospective association between healthy lifestyle behaviors and objectively measured physical function in midlife women. METHODS: Participants included 1769 racially/ethnically diverse women, ages 56-68 yr, from the Study of Women's Health Across the Nation cohort. Physical function was assessed at the 13th follow-up visit with the Short Physical Performance Battery (4-m walk, repeated chair stands, and balance test) and grip strength. A healthy lifestyle score (HLS), which ranged from 0 to 6, was calculated by averaging as many as three repeated measures of self-reported smoking, physical activity, and diet, all assessed before the 13th follow-up. Multivariable linear and logistic regressions modeled each component of physical performance as a function of HLS and, in separate models, of each lifestyle behavior, adjusted for the other behaviors. RESULTS: In multivariable analyses, the time for the 4-m walk was 0.06 s faster (P = 0.001) for every 1 point increase in the HLS. The time for the repeated chair stands was significantly shorter by approximately 0.20 s. Neither grip strength nor balance problems were significantly associated with the HLS (P = 0.28 and P = 0.19, respectively). The model examining the individual health behaviors showed that only physical activity was significantly associated with physical performance. CONCLUSION: Regular physical activity in early midlife has the potential to reduce the likelihood of physical functional limitations later in midlife.

Behavioral Interventions to Improve Asthma Outcomes for Adolescents: A Systematic Review.

BACKGROUND: Factors at multiple ecological levels, including the child, family, home, medical care, and community, impact adolescent asthma outcomes. OBJECTIVE: This systematic review characterizes behavioral interventions at the child, family, home, medical system, and community level to improve asthma management among adolescents. METHODS: A systematic search of PubMed, SCOPUS, OVID, PsycINFO, CINAHL, and reference review databases was conducted from January 1, 2000, through August 10, 2014. Articles were included if the title or abstract included asthma AND intervention AND (education OR self-management OR behavioral OR technology OR trigger reduction), and the mean and/or median age of participants was between 11 and 16 years. We compared populations, intervention characteristics, study designs, outcomes, settings, and intervention levels across studies to evaluate behavioral interventions to improve asthma management for adolescents. RESULTS: Of 1230 articles identified and reviewed, 24 articles (21 unique studies) met inclusion criteria. Promising approaches to improving adherence to daily controller medications include objective monitoring of inhaled corticosteroid adherence with allergist and/or immunologist feedback on medication-taking behavior and school nurse directly observed therapy. Efficacy at increasing asthma self-management skills was demonstrated using group interactive learning in the school setting. This systematic review is not a meta-analysis, thus limiting its quantitative assessment of studies. Publication bias may also limit our findings. CONCLUSIONS: Novel strategies to objectively increase controller medication adherence for adolescents include allergist and/or immunologist feedback and school nurse directly observed therapy. Schools, the most common setting across studies in this review, provide the opportunity for group interactive learning to improve asthma knowledge and self-management skills.

Design of a lifestyle intervention to slow menopause-related progression of intra-abdominal adipose tissue in women: The Women in the Southside Health and Fitness (WISHFIT) study.

BACKGROUND: Changes in reproductive hormones during menopause are associated with accumulation of intra-abdominal adipose tissue (IAAT), a subclinical indicator of cardiometabolic disease risk. Independent of reproductive hormones, unhealthy lifestyle contributes to IAAT gain. The Women in the Southside Health and Fitness (WISHFIT) Study aims to develop a lifestyle approach to slowing IAAT accumulation as women begin the menopausal transition. METHODS: The primary aim is to develop and conduct a proof-of-concept test of a multi-component, multi-level behavioral intervention targeting jointly physical activity, diet, and psychological well-being. Participants attend group sessions over 2 years to experiment with healthy living through both experiential and didactic learning, cultivate a health network, and draw on community resources to sustain change. The primary endpoint is 2-year IAAT progression, assessed using computerized tomography. Behavioral targets of treatment and secondary endpoints will be evaluated at 6, 12, 18 and 24 months. Change in social networks and community support will be assessed at 2 years. RESULTS: WISHFIT recruited 71 pre- and peri-menopausal Caucasian and African American women (mean ± SD age = 47.6 ± 3.4 yrs; BMI = 33.6 ± 7.3 kg/m2; 52% African American). Baseline IAAT was 2104.1 ± 1201.3 cm3. IAAT, physical activity, BMI, and self-reported family income and resilience differed by ethnicity at baseline. CONCLUSIONS: WISHFIT is a multi-component, multi-level intervention aimed at producing a sustained improvement in physical activity, diet, and psychological well-being early in the menopausal transition to slow menopause-related accumulation of IAAT. It provides a model for the process of developing a behavioral treatment to manage a chronic disease.

Group dynamics are associated with weight loss in the behavioral treatment of obesity.

OBJECTIVE: To assess whether group dynamics are associated with weight loss, session attendance, and self-monitoring adherence after 6 months of lifestyle intervention for obesity. METHODS: Women with obesity (N = 125; mean ± SD BMI = 37.84 ± 3.94 kg/m(2) ; age = 51.99 ± 10.81 years) participated in a 24-week group-based lifestyle weight loss intervention and achieved a weight loss of 9.13 ± 7.15 kg after 6 months. Participants reported their perceptions of group conflict, avoidance, engagement, social support, and attraction at the end of treatment. Multiple regression with forward selection assessed which group dynamic variables were associated with weight loss, attendance, and adherence. RESULTS: Greater perceived group conflict was associated with smaller weight losses (ß = 1.833, P = 0.044) and lower attendance (ß = -2.313, P = 0.002) and adherence rates (ß = -2.261, P = 0.030). Higher group attraction was associated with higher attendance rates (ß = 0.051, P = 0.039). The association between perceived conflict and weight change was mediated by attendance and adherence (P = 0.019). CONCLUSIONS: Findings demonstrate that group dynamics associate with weight loss outcomes, attendance, and adherence. Addressing conflicts and fostering acceptance among group members may promote success in group-based lifestyle interventions for obesity.

Associations between body mass index and sexual functioning in midlife women: the Study of Women's Health Across the Nation.

OBJECTIVE: This study aims to examine baseline and longitudinal associations between body mass index (BMI) and sexual functioning in midlife women. METHODS: Midlife women (N = 2,528) from the Study of Women's Health Across the Nation reported on sexual functioning and underwent measurements of BMI annually beginning in 1995-1997, with follow-up spanning 13.8 years. Associations between baseline levels and longitudinal changes in BMI and sexual desire, arousal, intercourse frequency, and ability to climax were assessed with generalized linear mixed-effects models. Models were adjusted for demographic variables, depressive symptoms, hormone therapy use, alcohol intake, menopause status, smoking status, and health status. RESULTS: Mean BMI increased from 27.7 to 29.1 kg/m2, whereas all sexual functioning variables declined across time (P values ≤ 0.001). Higher baseline BMI was associated with less frequent intercourse (P = 0.003; 95% CI, -0.059 to -0.012). Although overall change in BMI was not associated with changes in sexual functioning, years of greater-than-expected BMI increases relative to women's overall BMI change trajectory were characterized by less frequent intercourse (P < 0.001; 95% CI, -0.106 to -0.029) and reduced sexual desire (P = 0.020; 95% CI, -0.078 to -0.007). CONCLUSIONS: Although women's overall BMI change across 13.8 years of follow-up was not associated with overall changes in sexual functioning, sexual desire and intercourse frequency diminished with years of greater-than-expected weight gain. Results suggest that adiposity and sexual functioning change concurrently from year to year. Further research should explore the impact of weight management interventions as a strategy for preserving sexual functioning in midlife women.

Meal preparation and cleanup time and cardiometabolic risk over 14 years in the Study of Women's Health Across the Nation (SWAN).

OBJECTIVE: To determine whether baseline levels and longitudinal changes in meal preparation and cleanup time are associated with changes in cardiometabolic risk factors in midlife women. METHODS: Subjects were 2755 midlife women enrolled in the Study of Women's Health Across the Nation, a multi-ethnic, longitudinal cohort study in the United States. The five diagnostic components of the metabolic syndrome and meal preparation/cleanup time were assessed repeatedly across 14 years of follow-up (spanning 1996-2011) at seven U.S. sites. Mixed-effects logistic and ordered logistic models tested associations between meal preparation/cleanup time and odds of meeting criteria for metabolic syndrome and its individual diagnostic components. RESULTS: Women who spent more time preparing and cleaning up meals at baseline, or demonstrated greater increases in this activity, had greater increases over time in their odds of having metabolic syndrome and in the number of metabolic syndrome components for which they met criteria. Adjusted associations were observed between meal preparation/cleanup time and hypertension, impaired fasting glucose, hypertriglyceridemia, and low high-density lipoprotein cholesterol, but not abdominal obesity. CONCLUSIONS: In midlife women, greater meal preparation/cleanup time is associated with the development of an adverse cardiometabolic risk profile. Public health interventions should place greater emphasis on cooking healthfully, not just cooking frequently.

A randomized trial comparing weight loss treatment delivered in large versus small groups.

BACKGROUND: Behavioral interventions for obesity are commonly delivered in groups, although the effect of group size on weight loss has not been empirically evaluated. This behavioral weight loss trial compared the 6- and 12-month weight changes associated with interventions delivered in a large group (LG) or small groups (SG). METHODS: Obese adults (N = 66; mean age = 50 years; mean BMI = 36.5 kg/m2; 47% African American; 86% women) recruited from a health maintenance organization were randomly assigned to: (1) LG treatment (30 members/group), or (2) SG treatment (12 members/group). Conditions were comparable in frequency and duration of treatment, which included 24 weekly group sessions (months 1-6) followed by six monthly extended care contacts (months 7-12). A mixed effects model with unstructured covariance matrix was applied to analyze the primary outcome of weight change while accounting for baseline weight and dependence among participants' measurements over time. RESULTS: SG participants lost significantly more weight than LG participants at Month 6 (-6.5 vs. -3.2 kg; p = 0.03) and Month 12 (-7.0 vs. -1.7 kg; p < 0.002). SG participants reported better treatment engagement and self-monitoring adherence at Months 6 and 12, ps < 0.04, with adherence fully mediating the relationship between group size and weight loss. CONCLUSIONS: Receiving obesity treatment in smaller groups may promote greater weight loss and weight loss maintenance. This effect may be due to improved adherence facilitated by SG interactions. These novel findings suggest that the perceived efficiency of delivering behavioral weight loss treatment to LGs should be balanced against the potentially better outcomes achieved by a SG approach.

Dietary self-monitoring and long-term success with weight management.

OBJECTIVE: To examine the contributions of frequency, consistency, and comprehensiveness of dietary self-monitoring to long-term weight change. METHODS: Participants included 220 obese women (mean ± SD, age = 59.3 ± 6.1 years; BMI = 36.8 ± 4.9 kg/m(2) ) who achieved a mean weight loss of -10.39 ± 5.28% from baseline during 6 months of behavioral treatment and regained 2.30 ± 7.28% during a 12-month extended-care period. The contributions of cumulative frequency of self-monitoring (total number of food records), consistency across time (number of weeks with ≥3 records), and comprehensiveness of information recorded were examined as predictors of weight regain in a hierarchical linear regression analysis. The mediating role of adherence to daily caloric intake goals was tested using a bootstrapping analysis. RESULTS: The association between high total frequency of self-monitoring and reduced weight regain was moderated by weekly consistency of self-monitoring, P = 0.004; increased frequency produced beneficial effects on weight change only when coupled with high consistency (>3 days/week). There was no impact of comprehensiveness on weight change, P > 0.05. The favorable effect of high frequency/high consistency self-monitoring on weight change was partially mediated by participants' success in meeting daily caloric intake goals (P < 0.001). CONCLUSION: The combination of high frequency plus high consistency of dietary self-monitoring improves long-term success in weight management.

Mindfulness meditation as an intervention for binge eating, emotional eating, and weight loss: a systematic review.

Mindfulness-based approaches are growing in popularity as interventions for disordered eating and weight loss. Initial research suggests that mindfulness meditation may be an effective intervention for binge eating; however, no systematic review has examined interventions where mindfulness meditation was the primary intervention and no review has examined its effect on subclinical disordered eating or weight. Using the PRISMA method for systematic reviews, we reviewed 14 studies that investigated mindfulness meditation as the primary intervention and assessed binge eating, emotional eating, and/or weight change. Results suggest that mindfulness meditation effectively decreases binge eating and emotional eating in populations engaging in this behavior; evidence for its effect on weight is mixed. Additional research is warranted to determine comparative effectiveness and long-term effects of mindfulness training.

Dietary self-monitoring in patients with obstructive sleep apnea.

Self-monitoring of food intake is a cornerstone of behavioral weight loss interventions, but its use has not been evaluated in the treatment of obese patients with obstructive sleep apnea (OSA). This pilot study described patterns of adherence to dietary self-monitoring in obese patients with OSA and determined associations between self-monitoring and weight loss, psychosocial functioning, and adherence to continuous positive airway pressure treatment. Participants completed a 6-week behavioral weight loss intervention focused on dietary self-monitoring. Approximately one-third of participants were adherent to self-monitoring throughout the course of the intervention and experienced more weight loss than those who did not self-monitor regularly. More frequent dietary self-monitoring also appeared to be associated with adherence to other health behaviors. These preliminary data suggest that use of dietary self-monitoring may be beneficial for promoting weight loss and adherence to other important health behaviors in OSA patients.

Food insecurity is linked to a food environment promoting obesity in households with children.

OBJECTIVE: To determine the extent to which the presence and accessibility of healthful and less healthful foods in children's homes vary with level of food security. METHODS: A total of 41 parents or primary caregivers who had at least 1 child ages 2-13 and resided in a low-income area with limited food access completed a home food inventory and a validated measure assessing household food security. RESULTS: Compared with food-secure participants, marginal or low/very low food-secure caregivers reported significantly more obesity-promoting foods in the home, more microwavable or quick-cook frozen foods, and greater access to less healthful foods in the kitchen (all Ps < .05). CONCLUSIONS AND IMPLICATIONS: Given the greater presence and accessibility of less healthful foods, targeting home food environment may improve diet quality and health status in children of low-income, food insecure households.

Beverages contribute extra calories to meals and daily energy intake in overweight and obese women.

Caloric beverages may promote obesity by yielding energy without producing satiety, but prior laboratory and intervention studies are inconclusive. This study examined whether the diets of free-living overweight and obese women show evidence that calories from beverages are offset by reductions in solid food within individual eating occasions and across entire days. Eighty-two women weighed and recorded all consumed foods and beverages for seven days. Beverages were coded as high-calorie (≥ 0.165 kcal/g) or low-calorie (<0.165 kcal/g), and total energy intake and energy intake from solid food were calculated for each eating occasion and day. In covariate-adjusted models, energy intake from solid food did not differ between eating occasions that included high-calorie or low-calorie beverages and those with no reported beverage. Energy intake from solid food was also unrelated to the number of high-calorie or low-calorie beverages consumed per day. On average, eating occasions that included a high-calorie beverage were 169 kcal higher in total energy than those with no reported beverage, and 195 kcal higher in total energy than those that included a low-calorie beverage. Each high-calorie beverage consumed per day contributed an additional 147 kcal to women's daily energy intake, whereas low-calorie beverage intake was unrelated to daily energy intake. Beverages contributed to total energy intake in a near-additive fashion among free-living overweight and obese women, suggesting a need to develop more effective interventions to reduce caloric beverage intake in the context of weight management, and to potentially reexamine dietary guidelines.

Feasibility and acceptability of Internet grocery service in an urban food desert, Chicago, 2011-2012.

We explored the feasibility and acceptability of an Internet grocery service (IGS) as an approach to improving food access in urban neighborhoods. In our pilot study, caregivers residing in a documented Chicago food desert (N = 34, 79% ethnic minority) received a voucher to use a commercial IGS to purchase groceries for their household. Caregivers most frequently purchased fruits, vegetables, meats, and caloric beverages, and endorsed 4 factors as potentially important determinants of future IGS use. IGS programs could have a role in improving urban food access if they have competitive prices, provide rapid delivery, and incorporate strategies to discourage purchasing of discretionary caloric beverages.

Effects of prescribing 1,000 versus 1,500 kilocalories per day in the behavioral treatment of obesity: a randomized trial.

OBJECTIVE: Controversy exists regarding the optimal energy prescription to promote successful long-term behavioral management of obesity. Prescribing intake of 1,000 (vs. 1,500) kcal/day may produce larger initial weight reduction, but long-term advantage remains unclear. The effects of prescribing 1,000 versus 1,500 kcal/day on 6- and 12-month weight changes within behavioral treatment of obesity were examined. DESIGN AND METHODS: Participants were 125 obese women (mean ± SD; BMI = 37.84 ± 3.94 kg/m(2) ) randomly assigned goals of 1,000 or 1,500 kcal/day. RESULTS: From months 0 to 6, participants prescribed 1,000 kcal/day lost more weight than those prescribed 1,500 kcal/day (mean ± SE = -10.03 ± 0.92g vs. -6.23 ± 0.94 kg, P = 0.045); however, from months 7 through 12, only the 1,000 kcal/day condition experienced a significant weight regain (1.51 ± 0.77 kg, P = 0.025). Baseline caloric consumption moderated the effect of treatment on regain; participants with baseline intakes ≧2,000 kcal/day who were assigned 1,000 kcal/day were significantly more susceptible to weight regain than those assigned 1,500 kcal/day (P = 0.049). At month 12, a significantly greater percentage of 1,000 kcal/day participants achieved weight reductions of 5% or more than those prescribed 1,500 kcal/day. CONCLUSION: Encouraging obese individuals in behavioral treatment to adhere to a 1,000 kcal/day intake may increase their likelihood of achieving clinically meaningful weight losses.

Confirmatory factor analysis of the Beck Depression Inventory-II in bariatric surgery candidates.

Screening for depression is an integral part of psychological evaluations conducted prior to bariatric surgery. The Beck Depression Inventory-II (BDI-II) is the most commonly used measure of depression in these treatment evaluations. The reliability and validity of the BDI-II has not yet been evaluated within bariatric surgery-seeking samples, evidencing a significant gap in the present literature. The purpose of the present study is to evaluate the structural validity of the BDI-II and to examine the reliability and convergent and criterion validity of this instrument within a bariatric surgery-seeking sample. The study population consisted of 505 ethnically diverse bariatric surgery candidates presenting for presurgical psychological evaluations in a midwestern urban academic medical center. Confirmatory factor analytic results indicated that a 3-factor model consisting of affective, cognitive, and somatic factors was the best fitting model of depression within this sample. Internal consistency reliability was satisfactory for each subscale, ranging from .72 to .82. Moderate to large correlations were observed between each BDI-II subscale and a measure of depression previously validated with bariatric surgery candidates indicating adequate convergent validity. On the basis of clinical interview, 14% of the sample was diagnosed with current major depression. Significant mean differences were observed between depressed and nondepressed patients with respect to each BDI-II subscale score, demonstrating criterion-related validity. The BDI-II is a reliable and valid measure of depression for bariatric surgery candidates. Understanding the factor structure of the BDI-II can be useful for planning potential presurgical psychological interventions.

The association between rate of initial weight loss and long-term success in obesity treatment: does slow and steady win the race?

BACKGROUND: Controversy exists regarding the optimal rate of weight loss for long-term weight management success. PURPOSE: This study examined whether gradual initial weight loss was associated with greater long-term weight reduction than rapid initial loss. METHODS: Groups were drawn from participants in the TOURS trial, which included a sample of middle-aged (mean = 59.3 years) obese women (mean BMI = 36.8) who received a 6-month lifestyle intervention followed by a 1-year extended care program. Participants were encouraged to reduce caloric intake to achieve weight losses of 0.45 kg/week. Groups were categorized as "FAST" (> or =0.68 kg/week, n = 69), "MODERATE" (> or =0.23 and <0.68 kg/week, n = 104), and "SLOW" (<0.23 kg/week, n = 89) based on rate of weight loss during first month of treatment. RESULTS: The FAST, MODERATE, and SLOW groups differed significantly in mean weight changes at 6 months (-13.5, -8.9, and -5.1 kg, respectively, ps < 0.001), and the FAST and SLOW groups differed significantly at 18 months (-10.9, -7.1, and -3.7 kg, respectively, ps < 0.001). No significant group differences were found in weight regain between 6 and 18 months (2.6, 1.8, and 1.3 kg, respectively, ps < 0.9). The FAST and MODERATE groups were 5.1 and 2.7 times more likely to achieve 10% weight losses at 18 months than the SLOW group. CONCLUSION: Collectively, findings indicate both short- and long-term advantages to fast initial weight loss. Fast weight losers obtained greater weight reduction and long-term maintenance, and were not more susceptible to weight regain than gradual weight losers.

Morphine, nortriptyline and their combination vs. placebo in patients with chronic lumbar root pain.

Although lumbar radicular pain is the most common chronic neuropathic pain syndrome, there have been few randomized studies of drug treatments. We compared the efficacy of morphine (15-90 mg), nortriptyline (25-100 mg), their combination, and a benztropine "active placebo" (0.25-1 mg) in patients with chronic sciatica. Each period consisted of 5 weeks of dose escalation, 2 weeks of maintenance at the highest tolerated doses, and 2 weeks of dose tapering. The primary outcome was the mean daily leg pain score on a 0-10 scale during the maintenance period. Secondary outcomes included a 6-point ordinal global pain relief scale, the Beck Depression Inventory (BDI), the Oswestry Back Pain Disability Index (ODI) and the SF-36. In the 28 out of 61 patients who completed the study, none of the treatments produced significant reductions in average leg pain or other leg or back pain scores. Pain reduction, relative to placebo treatment was, 14% for nortriptyline (95% CI=[-2%, 30%]), 7% for morphine (95% CI=[-8%, 22%]), and 7% for the combination treatment (95% CI=[-4%, 18%]). Mean doses were: nortriptyline alone, 84+/-24.44 (SD) mg/day; morphine alone, 62+/-29 mg/day; and combination, morphine, 49+/-27 mg/day plus nortriptyline, 55 mg+/-33.18 mg/day. Over half of the study completers reported some adverse effect with morphine, nortriptyline or their combination. Within the limitations of the modest sample size and high dropout rate, these results suggest that nortriptyline, morphine and their combination may have limited effectiveness in the treatment of chronic sciatica.

Effects of chronic osteoarthritis pain on neuroendocrine function in men.

CONTEXT: Chronic pain has been associated with elevated cortisol, reduced LH and testosterone (T), and/or augmented circulating or excreted catecholamines. Most endocrine studies have been conducted in patients in whom the potentially confounding effects of depression, inflammatory disease, or coexistent medication use have not been controlled. OBJECTIVE: The objective of the study was to test the hypothesis that chronic pain activates ACTH-cortisol and suppresses LH-T. DESIGN AND SETTING: This was a case control study conducted at a clinical research center. PARTICIPANTS: Participants included 16 opioid-naive men with chronic osteoarthritis pain, aged 35-65 yr with body mass index 20-30 kg/m2, and 12 healthy, opioid- and pain-free men of similar ages and body mass indexes. METHODS: We compared circulating concentrations of ACTH, cortisol, LH, and T derived from every 20-min blood sampling (2000-0800 h), and 24-h urinary excretion of cortisol, epinephrine, norepinephrine, and dopamine. RESULTS: There were no significant differences in mean or integrated concentrations of ACTH, cortisol, LH, or T, or in the corresponding approximate entropy scores in osteoarthritis patients, compared with control subjects. The 0800-h serum LH concentrations were elevated in patients vs. controls (6.42 +/- 1.65 vs. 3.99 +/- 1.54 IU/liter, mean +/- sd, P = 0.02), whereas there were no significant group differences in total or free T, SHBG, cortisol binding globulin, dehydroepiandrosterone sulfate, or urinary cortisol and catecholamines. CONCLUSIONS: These data suggest that neuroendocrine function is not significantly altered in otherwise healthy men with chronic musculoskeletal pain and that prior reports of such hormonal abnormalities may have resulted from the confounding effects of coexistent illness or medication use.

Increased glucose tolerance and reduced adiposity in the absence of fasting hypoglycemia in mice with liver-specific Gs alpha deficiency.

The G protein G(s)alpha is essential for hormone-stimulated cAMP generation and is an important metabolic regulator. We investigated the role of liver G(s)-signaling pathways by developing mice with liver-specific G(s)alpha deficiency (LGsKO mice). LGsKO mice had increased liver weight and glycogen content and reduced adiposity, whereas survival, body weight, food intake, and metabolic rates at ambient temperature were unaffected. LGsKO mice had increased glucose tolerance with both increased glucose-stimulated insulin secretion and increased insulin sensitivity in liver and muscle. Fed LGsKO mice were hypoglycemic and hypoinsulinemic, with low expression of hepatic gluconeogenic enzymes and PPARgamma coactivator-1. However, LGsKO mice maintained normal fasting glucose and insulin levels, probably due to prolonged breakdown of glycogen stores and possibly increased extrahepatic gluconeogenesis. Lipid metabolism was unaffected in fed LGsKO mice, but fasted LGsKO mice had increased lipogenic and reduced lipid oxidation gene expression in liver and increased serum triglyceride and FFA levels. LGsKO mice had very high serum glucagon and glucagon-like peptide-1 levels and pancreatic alpha cell hyperplasia, probably secondary to hepatic glucagon resistance and/or chronic hypoglycemia. Our results define novel roles for hepatic G(s)-signaling pathways in glucose and lipid regulation, which may prove useful in designing new therapeutic targets for diabetes and obesity.