Change search
Link to record
Permanent link

Direct link
de Jong, Jasper M. A.ORCID iD iconorcid.org/0000-0001-8044-5410
Alternative names
Publications (10 of 17) Show all publications
Speakman, J. R., de Jong, J. M. A., Westerterp, K. R., Yamada, Y., Sagayama, H., Kurpad, A., . . . Wong, W. W. (2023). Total daily energy expenditure has declined over the past three decades due to declining basal expenditure, not reduced activity expenditure. Nature Metabolism, 5(4), 579-588
Open this publication in new window or tab >>Total daily energy expenditure has declined over the past three decades due to declining basal expenditure, not reduced activity expenditure
Show others...
2023 (English)In: Nature Metabolism, E-ISSN 2522-5812, Vol. 5, no 4, p. 579-588Article in journal (Refereed) Published
Abstract [en]

Obesity is caused by a prolonged positive energy balance. Whether reduced energy expenditure stemming from reduced activity levels contributes is debated. Here we show that in both sexes, total energy expenditure (TEE) adjusted for body composition and age declined since the late 1980s, while adjusted activity energy expenditure increased over time. We use the International Atomic Energy Agency Doubly Labelled Water database on energy expenditure of adults in the United States and Europe (n = 4,799) to explore patterns in total (TEE: n = 4,799), basal (BEE: n = 1,432) and physical activity energy expenditure (n = 1,432) over time. In males, adjusted BEE decreased significantly, but in females this did not reach significance. A larger dataset of basal metabolic rate (equivalent to BEE) measurements of 9,912 adults across 163 studies spanning 100 years replicates the decline in BEE in both sexes. We conclude that increasing obesity in the United States/Europe has probably not been fuelled by reduced physical activity leading to lowered TEE. We identify here a decline in adjusted BEE as a previously unrecognized factor. 

National Category
Endocrinology and Diabetes
Identifiers
urn:nbn:se:su:diva-220591 (URN)10.1038/s42255-023-00782-2 (DOI)000989676500009 ()37100994 (PubMedID)2-s2.0-85153922127 (Scopus ID)
Available from: 2023-08-31 Created: 2023-08-31 Last updated: 2023-08-31Bibliographically approved
Bokhari, M. H., Halleskog, C., Åslund, A., Boulet, N., Casadesús Rendos, E., de Jong, J. M., . . . Bengtsson, T. (2021). Isothermal microcalorimetry measures UCP1-mediated thermogenesis in mature brite adipocytes. Communications Biology, 4(1), Article ID 1108.
Open this publication in new window or tab >>Isothermal microcalorimetry measures UCP1-mediated thermogenesis in mature brite adipocytes
Show others...
2021 (English)In: Communications Biology, E-ISSN 2399-3642, Vol. 4, no 1, article id 1108Article in journal (Refereed) Published
Abstract [en]

The activation of thermogenesis in adipose tissue has emerged as an important target for the development of novel anti-obesity therapies. Using multi-well isothermal microcalorimetry, we have demonstrated that mature murine brown and brite adipocytes produce quantifiable heat upon β3-AR stimulation, independently of any anaerobic mechanisms. Additionally, in brite adipocytes lacking UCP1 protein, β3-AR stimulation still induces heat production, albeit to a much lower extent than in their wildtype counterparts, suggesting that UCP1 is an essential component of adrenergic induced thermogenesis in murine brite adipocytes exvivo. Similarly, we could observe an increase in heat production in human-derived adipocytes (hMADS) upon β-AR stimulation. Collectively, these results establish the use of isothermal microcalorimetry as a sensitive and accurate technique for measuring thermogenic responses in intact mature brite adipocytes from murine and human origin.

National Category
Biological Sciences
Identifiers
urn:nbn:se:su:diva-198698 (URN)10.1038/s42003-021-02639-4 (DOI)000697665400003 ()34548622 (PubMedID)
Available from: 2021-11-15 Created: 2021-11-15 Last updated: 2022-02-28Bibliographically approved
Cannon, B., de Jong, J. M. A., Fischer, A. W., Nedergaard, J. & Petrovic, N. (2020). Human brown adipose tissue: Classical brown rather than brite/beige?. Experimental Physiology, 105(8), 1191-1200
Open this publication in new window or tab >>Human brown adipose tissue: Classical brown rather than brite/beige?
Show others...
2020 (English)In: Experimental Physiology, ISSN 0958-0670, E-ISSN 1469-445X, Vol. 105, no 8, p. 1191-1200Article in journal (Refereed) Published
Abstract [en]

New Findings What is the topic of this review? It has been suggested that human brown adipose tissue (BAT) is more similar to the brite/beige adipose tissue of mice than to classical BAT of mice. The basis of this is discussed in relationship to the physiological conditions of standard experimental mice.

Keywords
beige fat, brown fat, thermoneutrality
National Category
Biological Sciences Cell and Molecular Biology
Identifiers
urn:nbn:se:su:diva-182885 (URN)10.1113/EP087875 (DOI)000536138300001 ()32378255 (PubMedID)
Available from: 2020-08-09 Created: 2020-08-09 Last updated: 2022-03-23Bibliographically approved
Fischer, A. W., de Jong, J. M. A., Sass, F., Schlein, C., Heeren, J. & Petrovic, N. (2020). Thermoneutrality-Induced Macrophage Accumulation in Brown Adipose Tissue Does Not Impair the Tissue's Competence for Cold-Induced Thermogenic Recruitment. Frontiers in Endocrinology, 11, Article ID 568682.
Open this publication in new window or tab >>Thermoneutrality-Induced Macrophage Accumulation in Brown Adipose Tissue Does Not Impair the Tissue's Competence for Cold-Induced Thermogenic Recruitment
Show others...
2020 (English)In: Frontiers in Endocrinology, E-ISSN 1664-2392, Vol. 11, article id 568682Article in journal (Refereed) Published
Abstract [en]

Brown adipose tissue from mice living under conditions approaching human thermal and nutritional conditions (prolonged exposure to thermoneutral temperature and to an energy-rich (high-fat, high-sugar) diet) - referred to as physiologically humanized mice, displays morphological and molecular characteristics significantly different from those observed in young, chow-fed mice maintained at room temperature - referred to as standard mice. Here, we further examined brown fat from physiologically humanized and standard mice, as well as from mice exposed to thermoneutrality for a long time but not to an energy-rich diet - referred to here as long-term thermoneutral mice. Global transcriptome analysis of brown fat revealed that genes that were the most upregulated in brown fat of thermoneutral mice (both physiologically humanized and long-term thermoneutral) were those related to inflammatory processes, including genes expressed selectively in macrophages. Cellular and molecular analyses confirmed that brown fat from thermoneutral mice was heavily infiltrated by macrophages, predominantly organized into crown-like structures. However, despite this, the brown fat of thermoneutral mice retained full competence to attain the greatest possible recruitment state and became macrophage-depleted during the process of cold acclimation. Thus, profound macrophage accumulation does not influence the thermogenic recruitment competence of brown fat.

Keywords
brown fat, thermogenic capacity, UCP1, macrophages, thermoneutrality
National Category
Cell and Molecular Biology
Identifiers
urn:nbn:se:su:diva-188202 (URN)10.3389/fendo.2020.568682 (DOI)000588782900001 ()33193086 (PubMedID)
Available from: 2020-12-29 Created: 2020-12-29 Last updated: 2024-01-17Bibliographically approved
de Jong, J. M. A., Sun, W., Pires, N. D., Frontini, A., Balaz, M., Jespersen, N. Z., . . . Petrovic, N. (2019). Human brown adipose tissue is phenocopied by classical brown adipose tissue in physiologically humanized mice. Nature Metabolism, 1(8), 830-843
Open this publication in new window or tab >>Human brown adipose tissue is phenocopied by classical brown adipose tissue in physiologically humanized mice
Show others...
2019 (English)In: Nature Metabolism, E-ISSN 2522-5812, Vol. 1, no 8, p. 830-843Article in journal (Refereed) Published
Abstract [en]

Human and rodent brown adipose tissues (BAT) appear morphologically and molecularly different. Here we compare human BAT with both classical brown and brite/beige adipose tissues of 'physiologically humanized' mice: middle-aged mice living under conditions approaching human thermal and nutritional conditions, that is, prolonged exposure to thermoneutral temperature (approximately 30 degrees C) and to an energy-rich (high-fat, high-sugar) diet. We find that the morphological, cellular and molecular characteristics (both marker and adipose-selective gene expression) of classical brown fat, but not of brite/beige fat, of these physiologically humanized mice are notably similar to human BAT. We also demonstrate, both in silico and experimentally, that in physiologically humanized mice only classical BAT possesses a high thermogenic potential. These observations suggest that classical rodent BAT is the tissue of choice for translational studies aimed at recruiting human BAT to counteract the development of obesity and its comorbidities.

National Category
Cell Biology Cell and Molecular Biology Physiology
Identifiers
urn:nbn:se:su:diva-177813 (URN)10.1038/s42255-019-0101-4 (DOI)000500745300010 ()
Available from: 2020-01-09 Created: 2020-01-09 Last updated: 2022-02-28Bibliographically approved
de Jong, J. M. A., Cannon, B. & Nedergaard, J. (2018). Promotion of lipid storage rather than of thermogenic competence by fetal versus newborn calf serum in primary cultures of brown adipocytes. Adipocyte, 7(3), 166-179
Open this publication in new window or tab >>Promotion of lipid storage rather than of thermogenic competence by fetal versus newborn calf serum in primary cultures of brown adipocytes
2018 (English)In: Adipocyte, ISSN 2162-3945, E-ISSN 2162-397X, Vol. 7, no 3, p. 166-179Article in journal (Refereed) Published
Abstract [en]

Much current understanding of brown adipocyte development comes from in-vitro cell models. Serum type may affect the behavior of cultured cells and thus conclusions drawn. Here, we investigate effects of serum type (fetal bovine versus newborn calf) on responses to differentiation inducers (the PPAR agonist rosiglitazone or the neurotransmitter norepinephrine) in cultured primary brown adipocytes. Lipid storage was enhanced by fetal versus newborn serum. However, molecular adipose conversion (Pparg2 and Fabp4 expression) was not affected by serum type. Rosiglitazone-induced (7-days) expression of thermogenic genes (i.e. Ucp1, Pgc1a, Dio2 and Elovl3) was not systematically affected by serum type. However, importantly, acute (2h) norepinephrine-induced thermogenic gene expression was overall markedly higher (and adipose genes somewhat lower) in cells cultured in newborn serum. Thus, newborn serum promotes thermogenic competence, and the use of fetal serum in brown adipocyte cultures (as is often routine) counteracts adequate differentiation. Agents that counteract this inhibition may therefore confoundingly be ascribed genuine thermogenic competence-inducing properties.

Keywords
brown adipocytes, thermogenesis, norepinephrine, UCP1, adipose conversion, differentiation, fetal bovine serum, newborn calf serum
National Category
Biological Sciences
Identifiers
urn:nbn:se:su:diva-162064 (URN)10.1080/21623945.2018.1479578 (DOI)000448600700003 ()29912625 (PubMedID)
Available from: 2018-11-27 Created: 2018-11-27 Last updated: 2022-03-23Bibliographically approved
de Jong, J. M. A., Wouters, R. T. F., Boulet, N., Cannon, B., Nedergaard, J. & Petrovic, N. (2017). The β3-adrenergic receptor is dispensable for browning of adipose tissues. American Journal of Physiology. Endocrinology and Metabolism, 312(6), E508-E518
Open this publication in new window or tab >>The β3-adrenergic receptor is dispensable for browning of adipose tissues
Show others...
2017 (English)In: American Journal of Physiology. Endocrinology and Metabolism, ISSN 0193-1849, E-ISSN 1522-1555, Vol. 312, no 6, p. E508-E518Article in journal (Refereed) Published
Abstract [en]

Brown and brite/beige adipocytes are attractive therapeutic targets to treat metabolic diseases. To maximally utilize their functional potential, further understanding is required about their identities and their functional differences. Recent studies with β3-adrenergic receptor knockout mice reported that brite/beige adipocytes, but not classical brown adipocytes, require the β3-adrenergic receptor for cold-induced transcriptional activation of thermogenic genes. We aimed to further characterize this requirement of the β3-adrenergic receptor as a functional distinction between classical brown and brite/beige adipocytes. However, when comparing wild-type and β3-adrenergic receptor knockout mice, we observed no differences in cold-induced thermogenic gene expression (Ucp1, Pgc1a, Dio2 and Cidea) in brown or white (brite/beige) adipose tissues. Irrespective of the duration of the cold exposure or the sex of the mice, we observed no effect of the absence of the β3-adrenergic receptor. Experiments with the β3-adrenergic receptor agonist CL-316,243 verified the functional absence of β3-adrenergic signaling in these knockout mice. The β3-adrenergic receptor knockout model in the present study was maintained on a FVB/N background, whereas earlier reports used C57BL/6 and 129Sv mice. Thus, our data imply background-dependent differences in adrenergic signaling mechanisms in response to cold exposure. Nonetheless, the present data indicate that the β3-adrenergic receptor is dispensable for cold-induced transcriptional activation in both classical brown and, as opposed to earlier studies, brite/beige cells. This should be taken into account in the increasing number of studies on the induction of browning and their extrapolation to human physiology.

Keywords
β3-adrenergic receptor, adipose browning, brown adipocytes, brite/beige adipocytes, UCP
National Category
Cell Biology
Research subject
Physiology
Identifiers
urn:nbn:se:su:diva-140882 (URN)10.1152/ajpendo.00437.2016 (DOI)000404391300005 ()28223294 (PubMedID)
Available from: 2017-03-21 Created: 2017-03-21 Last updated: 2022-02-28Bibliographically approved
Kalinovich, A. V., de Jong, J. M. A., Cannon, B. & Nedergaard, J. (2017). UCP1 in adipose tissues: two steps to full browning. Biochimie, 134, 127-137
Open this publication in new window or tab >>UCP1 in adipose tissues: two steps to full browning
2017 (English)In: Biochimie, ISSN 0300-9084, E-ISSN 1638-6183, Vol. 134, p. 127-137Article in journal (Refereed) Published
Abstract [en]

The possibility that brown adipose tissue thermogenesis can be recruited in order to combat the development of obesity has led to a high interest in the identification of "browning agents", i.e. agents that increase the amount and activity of UCP1 in brown and brite/beige adipose tissues. However, functional analysis of the browning process yields confusingly different results when the analysis is performed in one of two alternative steps. Thus, in one of the steps, using cold acclimation as a potent model browning agent, we find that if the browning process is followed in mice initially housed at 21 °C (the most common procedure), there is only weak molecular evidence for increases in UCP1 gene expression or UCP1 protein abundance in classical brown adipose tissue; however, in brite/beige adipose depots, there are large increases, apparently associating functional browning with events only in the brite/beige tissues. Contrastingly, in another step, if the process is followed starting with mice initially housed at 30 °C (thermoneutrality for mice, thus similar to normal human conditions), large increases in UCP1 gene expression and UCP1 protein abundance are observed in the classical brown adipose tissue depots; there is then practically no observable UCP1 gene expression in brite/beige tissues. This apparent conundrum can be resolved when it is realized that the classical brown adipose tissue at 21 °C is already essentially fully differentiated and thus expands extensively through proliferation upon further browning induction, rather than by further enhancing cellular differentiation. When the limiting factor for thermogenesis, i.e. the total amount of UCP1 protein per depot, is analyzed, classical brown adipose tissue is by far the predominant site for the browning process, irrespective of which of the two steps is analyzed. There are to date no published data demonstrating that alternative browning agents would selectively promote brite/beige tissues versus classical brown tissue to a higher degree than does cold acclimation. Thus, to restrict investigations to examine adipose tissue depots where only a limited part of the adaptation process occurs (i.e. the brite/beige tissues) and to use initial conditions different from the thermoneutrality normally experienced by adult humans may seriously hamper the identification of therapeutically valid browning agents. The data presented here have therefore important implications for the analysis of the potential of browning agents and the nature of human brown adipose tissue.

Keywords
Beige, Brite, Browning, Cold acclimation, UCP1
National Category
Cell Biology
Research subject
Physiology
Identifiers
urn:nbn:se:su:diva-140881 (URN)10.1016/j.biochi.2017.01.007 (DOI)000395217100016 ()28109720 (PubMedID)
Available from: 2017-03-21 Created: 2017-03-21 Last updated: 2022-03-23Bibliographically approved
de Jong, J. (2017). Who is Who in the Adipose Organ: A look at the Heterogeneity of Adipocyte Biology. (Doctoral dissertation). Stockholm: Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University
Open this publication in new window or tab >>Who is Who in the Adipose Organ: A look at the Heterogeneity of Adipocyte Biology
2017 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The increasing prevalence of obesity and related health complications, such as type 2 diabetes, cardiovascular disease and cancer, demands thorough investigation of the underlying processes. One of the key tissues investigated in this context is adipose tissue. It is becoming increasingly clear that adipose tissue is a very dynamic and heterogenic organ. This thesis provides an overview of various aspects of adipose biology that illustrate its heterogenic nature and describes my own scientific contributions to this field.

We typically distinguish between thermogenic, energy-expending brown adipocytes and energy-storing white adipocytes that are located in anatomically distinct adipose depots. In addition, brite (or beige) adipocytes are functionally thermogenic, but are located among white adipocytes.

Related to functional variation, adipocytes and adipose tissues display a wide range of morphological appearances. An additional property that illustrates the heterogeneity among adipose cells and depots is the variation of cellular responses to physiological cues, such as changes in diet or environmental temperature. Furthermore, the developmental origins of various adipose types display great heterogeneity, which may explain some of the functional and dynamic differences that are observed.

In line with the complexity of developmental origins, molecular markers that were initially proposed to distinguish between brown, brite/beige and white adipose subtypes have added to the notion that the composition of the adipose organ is much more complex than has long been appreciated.

My own work has contributed to the enhancement of our understanding of the heterogeneity of adipose subtypes. In particular, my findings related to marker gene expression patterns have led to increased appreciation of the complex nature of adipose gene expression patterns and the complications of translating results obtained in mice to humans. Some of my other contributions have increased the understanding of the differences and similarities in thermogenic adipose tissue functionality and dynamics. With cell culture studies, I have revealed new characteristics of pre-adipose cells from various depots that further add to the appreciation of the adipose heterogeneity.

Overall, this thesis provides an overview of important characteristics of the adipose organ, illustrating its heterogenic nature. Realization of this heterogeneity is of importance in order to properly study the adipose organ to ultimately understand how the adipose organ can be therapeutically targeted to effectively treat adipose-related diseases.

Place, publisher, year, edition, pages
Stockholm: Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, 2017. p. 92
Keywords
Adipose tissue, Adipocyte, Brown, White, Brite/Beige, Physiology
National Category
Physiology
Research subject
Physiology
Identifiers
urn:nbn:se:su:diva-140884 (URN)978-91-7649-742-5 (ISBN)978-91-7649-743-2 (ISBN)
Public defence
2017-04-28, Vivi Täckholmsalen (Q211), NPQ-huset, Svante Arrheniusväg 20, Stockholm, 10:00 (English)
Opponent
Supervisors
Note

At the time of the doctoral defense, the following papers were unpublished and had a status as follows: Paper 3: Manuscript. Paper 7: Manuscript. Paper 8: Manuscript.

Available from: 2017-04-05 Created: 2017-03-21 Last updated: 2022-02-28Bibliographically approved
Fischer, A. W., Hoefig, C. S., Abreu-Vieira, G., de Jong, J. M. A., Petrovic, N., Mittag, J., . . . Nedergaard, J. (2016). Leptin Raises Defended Body Temperature without Activating Thermogenesis. Cell Reports, 14(7), 1621-1631
Open this publication in new window or tab >>Leptin Raises Defended Body Temperature without Activating Thermogenesis
Show others...
2016 (English)In: Cell Reports, E-ISSN 2211-1247, Vol. 14, no 7, p. 1621-1631Article in journal (Refereed) Published
Abstract [en]

Leptin has been believed to exert its weight-reducing action not only by inducing hypophagia but also by increasing energy expenditure/thermogenesis. Leptin-deficient ob/ob mice have correspondingly been thought to be thermogenically limited and to show hypothermia, mainly due to atrophied brown adipose tissue (BAT). In contrast to these established views, we found that BAT is fully functional and that leptin treatment did not increase thermogenesis in wildtype or in ob/ob mice. Rather, ob/ob mice showed a decreased but defended body temperature (i. e., were anapyrexic, not hypothermic) that was normalized to wild-type levels after leptin treatment. This was not accompanied by increased energy expenditure or BAT recruitment but, instead, was mediated by decreased tail heat loss. The weight-reducing hypophagic effects of leptin are, therefore, not augmented through a thermogenic effect of leptin; leptin is, however, pyrexic, i. e., it alters centrally regulated thresholds of thermoregulatory mechanisms, in parallel to effects of other cytokines.

National Category
Biological Sciences
Identifiers
urn:nbn:se:su:diva-128471 (URN)10.1016/j.celrep.2016.01.041 (DOI)000370970200007 ()26876182 (PubMedID)
Available from: 2016-03-30 Created: 2016-03-29 Last updated: 2024-01-17Bibliographically approved
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0001-8044-5410

Search in DiVA

Show all publications