Regulation of human aldoketoreductase 1C3 (AKR1C3) gene expression in the adipose tissue

Svensson, Per‐Arne; Gabrielsson, Britt G.; Jernås, Margareta; Gummesson, Anders; Sjöholm, Kajsa

doi:10.2478/s11658-008-0025-6

Cited by 26 publications

(25 citation statements)

References 35 publications

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“…Gene expression was evaluated using the Human Genome U133Plus2.0 DNA microarray (Affymetrix). Preparation of cRNA and hybridization were performed according to standard Affymetrix protocols as previously described (21).…”

Section: Methodsmentioning

confidence: 99%

Gene expression in human brown adipose tissue

Svensson

Jernås²,

Sjöholm³

et al. 2011

Int J Mol Med

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Abstract. Brown adipose tissue (BAT) has profound effects on body weight and metabolism in rodents. Recent reports show that human adults have significant amounts of BAT. Our aim was to study the gene expression profile of human BAT. Biopsies of adipose tissue with brown-red color and subcutaneous white adipose tissue (WAT) were obtained from 24 patients undergoing surgery in the thyroid region. Intrascapular BAT and epididymal WAT biopsies were obtained from 10 mice. Expression was analyzed by DNA microarray, real-time PCR and immunohistochemistry. Using the expression of the brown adipocyte-specific gene uncoupling protein 1 (UCP1) as a marker, approximately half of the human brown-red adipose tissue biopsies taken in the thyroid region contained BAT, and the presence of cells with brown adipocyte morphology was also verified by histology. Microarray analysis of 9 paired human BAT and WAT samples showed that 17 genes had at least a 4-fold higher expression in BAT compared to WAT and five of them (CKMT1, KCNK3, COBL, HMGCS2, TGM2) were verified using real-time PCR (P<0.05 for all). In addition, immunohistochemistry showed that the UCP1, KCNK3 and CKMT1 proteins are expressed in brown adipocytes. Except for UCP1 and KCNK3, the genes overexpressed in human BAT were not overexpressed in mouse BAT compared to mouse WAT. Our analysis identified genes that are differentially expressed in human BAT compared to WAT. The results also show that there are species-specific differences in BAT gene expression and this emphasizes the need for further molecular characterization of human BAT to clarify the mechanisms involved in regulated heat production in humans.

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Section: Methodsmentioning

confidence: 99%

Gene expression in human brown adipose tissue

Svensson

Jernås²,

Sjöholm³

et al. 2011

Int J Mol Med

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“…PGFS had originally been purified from bovine lung (11) and characterized to be a bifunctional protein carrying both activities of PGH 2 9,11-endoperoxide reductase to produce PGF 2␣ from PGH 2 and PGD 2 11-ketoreductase, producing 9␣,11␤-PGF 2␣ from PGD 2 , in the presence of NADPH (28). Human 3␣-hydroxysteroid dehydrogenase type 2, which is classified as AKR1C3, was then identified as a PGFS (19) and its expression was demonstrated to be low in adipose tissue of obese subjects (29). However, the expression of Akr1c18, a mouse homolog of human Akr1c3, was negligible in 3T3-L1 cells (data not shown).…”

Section: Discussionmentioning

confidence: 99%

Suppression of Adipocyte Differentiation by Aldo-keto Reductase 1B3 Acting as Prostaglandin F2α Synthase

Fujimori

Ueno

Nagata

et al. 2010

Journal of Biological Chemistry

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Prostaglandin (PG) F 2␣ suppresses adipocyte differentiation by inhibiting the function of peroxisome proliferatoractivated receptor ␥. However, PGF 2␣ synthase (PGFS) in adipocytes remains to be identified. Here, we studied the expression of members of the aldo-keto reductase (AKR) 1B family acting as PGFS during adipogenesis of mouse 3T3-L1 cells. AKR1B3 mRNA was expressed in preadipocytes, and its level increased about 4-fold at day 1 after initiation of adipocyte differentiation, and then quickly decreased the following day to a level lower than that in the preadipocytes. In contrast, the mRNA levels of Akr1b8 and 1b10 were clearly lower than that level of Akr1b3 in preadipocytes and remained unchanged during adipogenesis. The transient increase in Akr1b3 during adipogenesis was also observed by Western blot analysis. The mRNA for the FP receptor, which is selective for PGF 2␣ , was also expressed in preadipocytes. Its level increased about 2-fold within 1 h after the initiation of adipocyte differentiation and was maintained at almost the same level throughout adipocyte differentiation. The small interfering RNA for Akr1b3, but not for Akr1b8 or 1b10, suppressed PGF 2␣ production and enhanced the expression of adipogenic genes such as peroxisome proliferator-activated receptor ␥, fatty acid-binding protein 4 (aP2), and stearoylCoA desaturase. Moreover, an FP receptor agonist, Fluprostenol, suppressed the expression of those adipogenic genes in 3T3-L1 cells; whereas an FP receptor antagonist, AL-8810, efficiently inhibited the suppression of adipogenesis caused by the endogenous PGF 2␣ . These results indicate that AKR1B3 acts as the PGFS in adipocytes and that AKR1B3-produced PGF 2␣ suppressed adipocyte differentiation by acting through FP receptors.

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“…Unlike the liver, much of this adaptation is reversed at the transition to weight maintenance, favoring a gene expression profile that would enhance energy conservation during weight maintenance and the repletion of energy stores during meals or periods of chronic overfeeding (21,34,90,122,125,222,239). Markers of oxidative stress and inflammatory cytokines, which are also known to suppress appetite and increase expenditure, decline (104,122,176).…”

Section: Adipose Tissue: An Expanding Empty Fuel Tank Primed For Fimentioning

confidence: 99%

“…6A). Regardless of overall adiposity, smaller adipocytes, compared with larger adipocytes, are more sensitive to the antilipolytic effects of insulin, exhibit a lower basal and catecholamine-induced lipolysis, have a lower rate of turnover of the stored lipid, and express genes favoring energy storage (25,146,222). Reducing the size of adipocytes with energy-restricted weight loss primes them to take up and store excess energy when overfeeding occurs.…”

Section: Adipose Tissue: An Expanding Empty Fuel Tank Primed For Fimentioning

confidence: 99%

Biology's response to dieting: the impetus for weight regain

MacLean

Bergouignan

Cornier

et al. 2011

American Journal of Physiology-Regulatory, Integrative and Comp

369

326

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Dieting is the most common approach to losing weight for the majority of obese and overweight individuals. Restricting intake leads to weight loss in the short term, but, by itself, dieting has a relatively poor success rate for long-term weight reduction. Most obese people eventually regain the weight they have worked so hard to lose. Weight regain has emerged as one of the most significant obstacles for obesity therapeutics, undoubtedly perpetuating the epidemic of excess weight that now affects more than 60% of U.S. adults. In this review, we summarize the evidence of biology's role in the problem of weight regain. Biology's impact is first placed in context with other pressures known to affect body weight. Then, the biological adaptations to an energy-restricted, low-fat diet that are known to occur in the overweight and obese are reviewed, and an integrative picture of energy homeostasis after long-term weight reduction and during weight regain is presented. Finally, a novel model is proposed to explain the persistence of the "energy depletion" signal during the dynamic metabolic state of weight regain, when traditional adiposity signals no longer reflect stored energy in the periphery. The preponderance of evidence would suggest that the biological response to weight loss involves comprehensive, persistent, and redundant adaptations in energy homeostasis and that these adaptations underlie the high recidivism rate in obesity therapeutics. To be successful in the long term, our strategies for preventing weight regain may need to be just as comprehensive, persistent, and redundant, as the biological adaptations they are attempting to counter. energy restriction; diet-induced obesity; obesity prone; weight loss; energy balance IN THE UNITED STATES, OVER 60% of adults and close to 20% of children are overweight or obese (35,174). A number of effective weight loss strategies are available, but most are only transiently effective over a period of 3 to 6 mo. Less than 20% of individuals that have attempted to lose weight are able to achieve and maintain a 10% reduction over a year (128). Over one-third of lost weight tends to return within the first year, and the majority is gained back within 3 to 5 years (3,246). A number of reasons have been proposed for the high incidence of weight regain (69,246), and several point to the biological response to weight loss.The objective of this review is to examine the role of this biological response in the process of weight regain. Biological regulation is first discussed in relation to other nonbiological pressures that affect body weight as weight is gained, lost, and regained. The specific biological adaptations to the most common form of dieting, an energy-restricted low-fat diet, are then discussed in more detail. Previous reviews provide extensive descriptions of the normal adaptive response to energy restriction. We do not attempt to recapitulate those efforts here. Rather, the unique perspective of this review summarizes those adaptations that have been confirmed o...

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Regulation of human aldoketoreductase 1C3 (AKR1C3) gene expression in the adipose tissue

Cited by 26 publications

References 35 publications

Gene expression in human brown adipose tissue

Gene expression in human brown adipose tissue

Suppression of Adipocyte Differentiation by Aldo-keto Reductase 1B3 Acting as Prostaglandin F2α Synthase

Biology's response to dieting: the impetus for weight regain

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