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  • 1.
    Cannon, Barbara
    et al.
    Stockholm University, Faculty of Science, The Wenner-Gren Institute , Physiology.
    Nedergaard, Jan
    Stockholm University, Faculty of Science, The Wenner-Gren Institute , Physiology.
    Metabolic consequences of the presence or absence of the thermogenic capacity of brown adipose tissue in mice (and probably in humans)2010In: International Journal of Obesity, ISSN 0307-0565, E-ISSN 1476-5497, Vol. 34, no 1, p. S7-S16Article in journal (Refereed)
    Abstract [en]

    Only with the development of the uncoupling protein 1 (UCP1)-ablated mouse has it become possible to strictly delineate the physiological significance of the thermogenic capacity of brown adipose tissue. Considering the presence of active brown adipose tissue in adult humans, these insights may have direct human implications. In addition to classical nonshivering thermogenesis, all adaptive adrenergic thermogeneses, including diet-induced thermogenesis, is fully dependent on brown adipocyte activity. Any weight-reducing effect of β(3)-adrenergic agonists is fully dependent on UCP1 activity, as is any weight-reducing effect of leptin (in excess of its effect on reduction of food intake). Consequently, in the absence of the thermogenic activity of brown adipose tissue, obesity develops spontaneously. The ability of brown adipose tissue to contribute to glucose disposal is also mainly related to thermogenic activity. However, basal metabolic rate, cold-induced thermogenesis, acute cold tolerance, fevers, nonadaptive adrenergic thermogenesis and processes such as angiogenesis in brown adipose tissue itself are not dependent on UCP1 activity. Whereas it is likely that these conclusions are also qualitatively valid for adult humans, the quantitative significance of brown adipose tissue for human metabolism--and the metabolic consequences for a single individual possessing more or less brown adipose tissue--awaits clarification.

  • 2. García-Carrizo, Francisco
    et al.
    Cannon, Barbara
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Nedergaard, Jan
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Picó, Catalina
    Dols, Albert
    Rodríguez, Ana María
    Palou, Andreu
    Regulation of thermogenic capacity in brown and white adipocytes by the prebiotic high-esterified pectin and its postbiotic acetate2020In: International Journal of Obesity, ISSN 0307-0565, E-ISSN 1476-5497, Vol. 44, no 3, p. 715-726Article in journal (Refereed)
    Abstract [en]

    Objectives High-esterified pectin (HEP) is a prebiotic able to modulate gut microbiota, associated with health-promoting metabolic effects in glucose and lipid metabolism and adipostatic hormone sensitivity. Possible effects regulating adaptive thermogenesis and energy waste are poorly known. Therefore, we aimed to study how physiological supplementation with HEP is able to affect microbiota, energy metabolism and adaptive thermogenic capacity, and to contribute to the healthier phenotype promoted by HEP supplementation, as previously shown. We also attempted to decipher some of the mechanisms involved in the HEP effects, including in vitro experiments.

    Subjects and experimental design We used a model of metabolic malprogramming consisting of the progeny of rats with mild calorie restriction during pregnancy, both under control diet and an obesogenic (high-sucrose) diet, supplemented with HEP, combined with in vitro experiments in primary cultured brown and white adipocytes treated with the postbiotic acetate.

    Results Our main findings suggest that chronic HEP supplementation induces markers of brown and white adipose tissue thermogenic capacity, accompanied by a decrease in energy efficiency, and prevention of weight gain under an obesogenic diet. We also show that HEP promotes an increase in beneficial bacteria in the gut and peripheral levels of acetate. Moreover, in vitro acetate can improve adipokine production, and increase thermogenic capacity and browning in brown and white adipocytes, respectively, which could be part of the protection mechanism against excess weight gain observed in vivo.

    Conclusion HEP and acetate stand out as prebiotic/postbiotic active compounds able to modulate both brown-adipocyte metabolism and browning and protect against obesity.

  • 3.
    Holowko, Natalie
    et al.
    Stockholm University, Faculty of Social Sciences, Centre for Health Equity Studies (CHESS). School of Population Health, University of Queensland.
    Mishra, Gita
    School of Population Health, University of Queensland.
    Koupil, Ilona
    Stockholm University, Faculty of Social Sciences, Centre for Health Equity Studies (CHESS).
    Social inequality in excessive gestational weight gain2014In: International Journal of Obesity, ISSN 0307-0565, E-ISSN 1476-5497, Vol. 38, no 1, p. 91-96Article in journal (Refereed)
    Abstract [en]

    Objective: 

    Optimal gestational weight gain (GWG) leads to better outcomes for both the mother and child, whereas excessive gains can act as a key stage for obesity development. Little is known about social inequalities in GWG. This study investigates the influence of education level on pre-pregnancy body mass index (BMI) and GWG.

    Design: 

    Register-based population study.

    Setting: 

    Sweden

    Participants: 

    Four thousand and eighty women born in Sweden who were a part of the third generation Uppsala Birth Cohort Study. Register data linkages were used to obtain information on social characteristics, BMI and GWG of women with singleton first births from 1982 to 2008.

    Main outcome measure: 

    Pre-pregnancy BMI and the Institute of Medicine’s (IOM) categories of GWG for a given pre-pregnancy BMI. Results were adjusted for calendar period, maternal age, living arrangements, smoking, history of chronic disease and pre-pregnancy BMI when appropriate.

    Results: 

    Although most women (67%) were of healthy pre-pregnancy BMI, 20% were overweight and 8% were obese. Approximately half of all women in the sample had excessive GWG, with higher pre-pregnancy BMI associated with higher risk of excessive GWG, regardless of education level; this occurred for 76% of overweight and 75% of obese women. Lower educated women with a healthy pre-pregnancy BMI were at greater risk of excessive GWG—odds ratio 1.76 (95% confidence interval 1.28–2.43) for elementary and odds ratio 1.32 (1.06–1.64) for secondary compared with tertiary educated, adjusted for age and birth year period. Nearly half of women with an elementary or secondary education (48%) gained weight excessively.

    Conclusion: 

    Education did not provide a protective effect in avoiding excessive GWG among overweight and obese women, of whom ~75% gained weight excessively. Lower educated women with a BMI within the healthy range, however, are at greater risk of excessive GWG. Health professionals need to tailor their pre-natal advice to different groups of women in order to achieve optimal pregnancy outcomes and avoid pregnancy acting as a stage in the development of obesity.

  • 4.
    Kalinovich, Anastasia V.
    et al.
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute. Lomonosov Moscow State University, Russian Federation.
    Mattsson, C. L.
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Youssef, M. R.
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Petrovic, Natasa
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Ost, M.
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Skulachev, V. P.
    Shabalina, Irina G.
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute. Lomonosov Moscow State University, Russian Federation.
    Mitochondria-targeted dodecyltriphenylphosphonium (C12TPP) combats high-fat-diet-induced obesity in mice2016In: International Journal of Obesity, ISSN 0307-0565, E-ISSN 1476-5497, Vol. 40, no 12, p. 1864-1874Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: A membrane-penetrating cation, dodecyltriphenylphosphonium (C12TPP), facilitates the recycling of fatty acids in the artificial lipid membrane and mitochondria. C12TPP can dissipate mitochondrial membrane potential and may affect total energy expenditure and body weight in animals and humans. METHODS: We investigated the metabolic effects of C12TPP in isolated brown-fat mitochondria, brown adipocyte cultures and mice in vivo. Experimental approaches included the measurement of oxygen consumption, carbon dioxide production, western blotting, magnetic resonance imaging and bomb calorimetry. RESULTS: In mice, C12TPP (50 mu mol per (day.kg body weight)) in the drinking water significantly reduced body weight (12%, P<0.001) and body fat mass (24%, P<0.001) during the first 7 days of treatment. C12TPP did not affect water palatability and intake or the energy and lipid content in feces. The addition of C12TPP to isolated brown-fat mitochondria resulted in increased oxygen consumption. Three hours of pretreatment with C12TPP also increased oligomycin-insensitive oxygen consumption in brown adipocyte cultures (P<0.01). The effects of C12TPP on mitochondria, cells and mice were independent of uncoupling protein 1 (UCP1). However, C12TPP treatment increased the mitochondrial protein levels in the brown adipose tissue of both wild-type and UCP1-knockout mice. Pair-feeding revealed that one-third of the body weight loss in C12TPP-treated mice was due to reduced food intake. C12TPP treatment elevated the resting metabolic rate (RMR) by up to 18% (P<0.05) compared with pair-fed animals. C12TPP reduced the respiratory exchange ratio, indicating enhanced fatty acid oxidation in mice. CONCLUSIONS: C12TPP combats diet-induced obesity by reducing food intake, increasing the RMR and enhancing fatty acid oxidation.

  • 5. Stenholm, Sari
    et al.
    Head, J.
    Aalto, V.
    Kivimäki, M.
    Kawachi, I.
    Zins, M.
    Goldberg, M.
    Platts, Loretta G.
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Zaninotto, P.
    Magnusson Hanson, Linda L.
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Westerlund, Hugo
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Vahtera, J.
    Body mass index as a predictor of healthy and disease-free life expectancy between ages 50 and 75: a multicohort study2017In: International Journal of Obesity, ISSN 0307-0565, E-ISSN 1476-5497, Vol. 41, no 5, p. 769-775Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: While many studies have shown associations between obesity and increased risk of morbidity and mortality, little comparable information is available on how body mass index (BMI) impacts health expectancy. We examined associations of BMI with healthy and chronic disease-free life expectancy in four European cohort studies.

    METHODS: Data were drawn from repeated waves of cohort studies in England, Finland, France and Sweden. BMI was categorized into four groups from normal weight (18.5-24.9 kg m(-2)) to obesity class II (⩾35 kg m(-2)). Health expectancy was estimated with two health indicators: sub-optimal self-rated health and having a chronic disease (cardiovascular disease, cancer, respiratory disease and diabetes). Multistate life table models were used to estimate sex-specific healthy life expectancy and chronic disease-free life expectancy from ages 50 to 75 years for each BMI category.

    RESULTS: The proportion of life spent in good perceived health between ages 50 and 75 progressively decreased with increasing BMI from 81% in normal weight men and women to 53% in men and women with class II obesity which corresponds to an average 7-year difference in absolute terms. The proportion of life between ages 50 and 75 years without chronic diseases decreased from 62 and 65% in normal weight men and women and to 29 and 36% in men and women with class II obesity, respectively. This corresponds to an average 9 more years without chronic diseases in normal weight men and 7 more years in normal weight women between ages 50 and 75 years compared to class II obese men and women. No consistent differences were observed between cohorts.

    CONCLUSIONS: Excess BMI is associated with substantially shorter healthy and chronic disease-free life expectancy, suggesting that tackling obesity would increase years lived in good health in populations.

  • 6. van Beek, Sten
    et al.
    Hashim, Dzhansel
    Bengtsson, Tore
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Hoeks, Joris
    Physiological and molecular mechanisms of cold-induced improvements in glucose homeostasis in humans beyond brown adipose tissue2023In: International Journal of Obesity, ISSN 0307-0565, E-ISSN 1476-5497, Vol. 47, no 5, p. 338-347Article, review/survey (Refereed)
    Abstract [en]

    Exposure to low ambient temperatures has previously been demonstrated to markedly improve glucose homeostasis in both rodents and humans. Although the brown adipose tissue is key in mediating these beneficial effects in rodents, its contribution appears more limited in humans. Hence, the exact tissues and underlying mechanisms that mediate cold-induced improvements in glucose homeostasis in humans remain to be fully established. In this review, we evaluated the response of the main organs involved in glucose metabolism (i.e. pancreas, liver, (white) adipose tissue, and skeletal muscle) to cold exposure and discuss their potential contribution to cold-induced improvements in glucose homeostasis in humans. We here show that cold exposure has widespread effects on metabolic organs involved in glucose regulation. Nevertheless, cold-induced improvements in glucose homeostasis appear primarily mediated via adaptations within the skeletal muscle and (presumably) white adipose tissue. Since the underlying mechanisms remain elusive, future studies should be aimed at pinpointing the exact physiological and molecular mechanisms involved in humans. Nonetheless, cold exposure holds great promise as a novel, additive lifestyle approach to improve glucose homeostasis in insulin resistant individuals.

  • 7.
    Virtanen, Marianna
    et al.
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. University of Eastern Finland, Finland.
    Jokela, Markus
    Lallukka, Tea
    Magnusson Hanson, Linda
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Pentti, Jaana
    Nyberg, Solja T.
    Alfredsson, Lars
    Batty, G. David
    Casini, Annalisa
    Clays, Els
    DeBacquer, Dirk
    Ervasti, Jenni
    Fransson, Eleonor
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden; Jönköping University, Sweden.
    Halonen, Jaana I.
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Finnish Institute of Occupational Health, Finland.
    Head, Jenny
    Kittel, France
    Knutsson, Anders
    Leineweber, Constanze
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Nordin, Maria
    Oksanen, Tuula
    Pietiläinen, Olli
    Rahkonen, Ossi
    Salo, Paula
    Singh-Manoux, Archana
    Stenholm, Sari
    Suominen, Sakari B.
    Theorell, Töres
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Vahtera, Jussi
    Westerholm, Peter
    Westerlund, Hugo
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Kivimäki, Mika
    Long working hours and change in body weight: analysis of individual-participant data from 19 cohort studies2020In: International Journal of Obesity, ISSN 0307-0565, E-ISSN 1476-5497, Vol. 44, no 6, p. 1368-1375Article in journal (Refereed)
    Abstract [en]

    Objective: To examine the relation between long working hours and change in body mass index (BMI).

    Methods: We performed random effects meta-analyses using individual-participant data from 19 cohort studies from Europe, US and Australia (n = 122,078), with a mean of 4.4-year follow-up. Working hours were measured at baseline and categorised as part time (<35 h/week), standard weekly hours (35–40 h, reference), 41–48 h, 49–54 h and ≥55 h/week (long working hours). There were four outcomes at follow-up: (1) overweight/obesity (BMI ≥ 25 kg/m2) or (2) overweight (BMI 25–29.9 kg/m2) among participants without overweight/obesity at baseline; (3) obesity (BMI ≥ 30 kg/m2) among participants with overweight at baseline, and (4) weight loss among participants with obesity at baseline.

    Results: Of the 61,143 participants without overweight/obesity at baseline, 20.2% had overweight/obesity at follow-up. Compared with standard weekly working hours, the age-, sex- and socioeconomic status-adjusted relative risk (RR) of overweight/obesity was 0.95 (95% CI 0.90–1.00) for part-time work, 1.07 (1.02–1.12) for 41–48 weekly working hours, 1.09 (1.03–1.16) for 49–54 h and 1.17 (1.08–1.27) for long working hours (Pfor trend <0.0001). The findings were similar after multivariable adjustment and in subgroup analyses. Long working hours were associated with an excess risk of shift from normal weight to overweight rather than from overweight to obesity. Long working hours were not associated with weight loss among participants with obesity.

    Conclusions: This analysis of large individual-participant data suggests a small excess risk of overweight among the healthy-weight people who work long hours.

  • 8. Wicklow, B. A.
    et al.
    Becker, A.
    Chateau, D.
    Palmer, Katie
    Stockholm University, Faculty of Social Sciences, Department of Psychology.
    Kozyrskij, A.
    Sellers, E. A. C.
    Comparison of anthropometric measurements in children to predict metabolic syndrome in adolescence: analysis of prospective cohort data2015In: International Journal of Obesity, ISSN 0307-0565, E-ISSN 1476-5497, Vol. 39, no 7, p. 1070-1078Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: The optimal screening measures for obesity in children remain controversial. Our study aimed to determine the anthropometric measurement at age 10 years that most strongly predicts the incidence of cardio-metabolic risk factors at age 13 years. SUBJECTS/METHODS: This was a prospective cohort study of a population-based cohort of 438 children followed between age 7 and 13 years of age. The main exposure variables were adiposity at age 10 years determined from body mass index (BMI) Z-score, waist circumference (WC) Z-score, waist-to-hip ratio and waist-to-height ratio. Outcome measures included systolic (SBP) and diastolic blood pressure (DBP), fasting high-density (HDL-c) and low-density lipoprotein cholesterol (LDL-c), triglycerides, insulin and glucose (homeostasis model of assessment, HOMA), and the presence of metabolic syndrome (MetS). RESULTS: WC Z-score at age 10 years was a stronger predictor of SBP (beta 0.21, R-2 0.38, P < 0.001 vs beta 0.30, R-2 0.20, P < 0.001) and HOMA (beta 0.51, R-2 0.25, P < 0.001 vs 0.40, R-2 0.19, P < 0.001) at age 13 years compared with BMI Z-score. WC relative to height and hip was stronger predictors of cardio-metabolic risk than BMI Z-score or WC Z-score. The relative risk (RR) of incident MetS was greater for an elevated BMI Z-score than for an elevated WC (girls: RR 2.52, 95% confidence interval (CI): 1.46-4.34 vs RR 1.56, 95% CI 1.18-2.07) and (boys: RR 2.86, 95% CI 1.79-4.62 vs RR 2.09, 95% CI 1.59-2.77). CONCLUSIONS: WC was a better predictor of SBP and HOMA compared with BMI or WC expressed relative to height or hip circumference. BMI was associated with higher odds of MetS compared with WC. Thus, BMI and WC may each be clinically relevant markers of different cardio-metabolic risk factors, and important in informing obesity-related prevention and treatment strategies.

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