Being able to effectively match energy intake to energy expenditure (EE) is an important aspect in preventing weight re-gain in the post-obese. Although it is generally agreed upon that resting EE decreases concomitantly with weight loss, there is no set standard comparing the deviations with differing weight loss protocols and additionally, controversy remains as to whether this decrease is greater than can predicted. In order to address these issues 2977 subjects were analyzed using a systematic review and the differences of both the protocol and length of various interventions in addition to sex were compared. Next, data was selected from this systematic review and 815 subjects were analyzed for weight loss-induced changes in resting EE, FM and FFM. Another subgroup of studies (n = 1450) was analyzed and compared against the Harris-Benedict prediction equation to determine whether the changes in resting EE were greater than what was expected. Finally, in order to determine which factors may be involved in regulating changes in resting EE during weight loss, a secondary analysis was performed on 28 post-menopausal women (age= 50.4 ± 2.0 yrs; BMI= 32.4 ± 5.2 kg/m²) who were submitted to a 6-month caloric restriction. Body composition (DXA), resting EE (indirect calorimetry), physical activity EE (PAEE) and total EE (TEE) (doubly-labelled water) were measured before and after the 6 month weight loss. Blood samples were collected before and after to measure leptin and peptide YY. The results indicate that there was indeed a depression in resting EE during weight loss regardless of the type of intervention utilized. Furthermore, these findings suggest that the changes could not fully be explained by changes of FM and FFM alone and that leptin may be an important contributor to the changes of resting EE during weight loss.

Being able to effectively match energy intake to energy expenditure (EE) is an important aspect in preventing weight re-gain in the post-obese. Although it is generally agreed upon that resting EE decreases concomitantly with weight loss, there is no set standard comparing the deviations with differing weight loss protocols and additionally, controversy remains as to whether this decrease is greater than can predicted. In order to address these issues 2977 subjects were analyzed using a systematic review and the differences of both the protocol and length of various interventions in addition to sex were compared. Next, data was selected from this systematic review and 815 subjects were analyzed for weight loss-induced changes in resting EE, FM and FFM. Another subgroup of studies (n = 1450) was analyzed and compared against the Harris-Benedict prediction equation to determine whether the changes in resting EE were greater than what was expected. Finally, in order to determine which factors may be involved in regulating changes in resting EE during weight loss, a secondary analysis was performed on 28 post-menopausal women (age= 50.4 ± 2.0 yrs; BMI= 32.4 ± 5.2 kg/m²) who were submitted to a 6-month caloric restriction. Body composition (DXA), resting EE (indirect calorimetry), physical activity EE (PAEE) and total EE (TEE) (doubly-labelled water) were measured before and after the 6 month weight loss. Blood samples were collected before and after to measure leptin and peptide YY. The results indicate that there was indeed a depression in resting EE during weight loss regardless of the type of intervention utilized. Furthermore, these findings suggest that the changes could not fully be explained by changes of FM and FFM alone and that leptin may be an important contributor to the changes of resting EE during weight loss.

Being able to effectively match energy intake to energy expenditure (EE) is an important aspect in preventing weight re-gain in the post-obese. Although it is generally agreed upon that resting EE decreases concomitantly with weight loss, there is no set standard comparing the deviations with differing weight loss protocols and additionally, controversy remains as to whether this decrease is greater than can predicted. In order to address these issues 2977 subjects were analyzed using a systematic review and the differences of both the protocol and length of various interventions in addition to sex were compared. Next, data was selected from this systematic review and 815 subjects were analyzed for weight loss-induced changes in resting EE, FM and FFM. Another subgroup of studies (n = 1450) was analyzed and compared against the Harris-Benedict prediction equation to determine whether the changes in resting EE were greater than what was expected. Finally, in order to determine which factors may be involved in regulating changes in resting EE during weight loss, a secondary analysis was performed on 28 post-menopausal women (age= 50.4 ± 2.0 yrs; BMI= 32.4 ± 5.2 kg/m²) who were submitted to a 6-month caloric restriction. Body composition (DXA), resting EE (indirect calorimetry), physical activity EE (PAEE) and total EE (TEE) (doubly-labelled water) were measured before and after the 6 month weight loss. Blood samples were collected before and after to measure leptin and peptide YY. The results indicate that there was indeed a depression in resting EE during weight loss regardless of the type of intervention utilized. Furthermore, these findings suggest that the changes could not fully be explained by changes of FM and FFM alone and that leptin may be an important contributor to the changes of resting EE during weight loss.

Being able to effectively match energy intake to energy expenditure (EE) is an important aspect in preventing weight re-gain in the post-obese. Although it is generally agreed upon that resting EE decreases concomitantly with weight loss, there is no set standard comparing the deviations with differing weight loss protocols and additionally, controversy remains as to whether this decrease is greater than can predicted. In order to address these issues 2977 subjects were analyzed using a systematic review and the differences of both the protocol and length of various interventions in addition to sex were compared. Next, data was selected from this systematic review and 815 subjects were analyzed for weight loss-induced changes in resting EE, FM and FFM. Another subgroup of studies (n = 1450) was analyzed and compared against the Harris-Benedict prediction equation to determine whether the changes in resting EE were greater than what was expected. Finally, in order to determine which factors may be involved in regulating changes in resting EE during weight loss, a secondary analysis was performed on 28 post-menopausal women (age= 50.4 ± 2.0 yrs; BMI= 32.4 ± 5.2 kg/m²) who were submitted to a 6-month caloric restriction. Body composition (DXA), resting EE (indirect calorimetry), physical activity EE (PAEE) and total EE (TEE) (doubly-labelled water) were measured before and after the 6 month weight loss. Blood samples were collected before and after to measure leptin and peptide YY. The results indicate that there was indeed a depression in resting EE during weight loss regardless of the type of intervention utilized. Furthermore, these findings suggest that the changes could not fully be explained by changes of FM and FFM alone and that leptin may be an important contributor to the changes of resting EE during weight loss.

Yoshinori Hiraoka, Tatsuhiko Matsuoka, Mikiko Ohno, Kazuhiro Nakamura, Sayaka Saijo, Shigenobu Matsumura, Kiyoto Nishi, Jiro Sakamoto, Po-Min Chen, Kazuo Inoue, Tohru Fushiki, Toru Kita, Takeshi Kimura & Eiichiro Nishi "Critical roles of nardilysin in the maintenance of body temperature homoeostasis" Nature Communications 5, Article number: 3224 doi:10.1038/ncomms4224 / 京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第18454号 / 医博第3909号 / 新制||医||1004(附属図書館) / 31332 / 京都大学大学院医学研究科医学専攻 / (主査)教授 渡邉 大, 教授 福田 和彦, 教授 瀬原 淳子 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

京都大学 / 新制・論文博士 / 博士(医学) / 乙第13490号 / 論医博第2258号 / 新制||医||1059(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 渡邉 大, 教授 稲垣 暢也, 教授 長船 健二 / 学位規則第4条第2項該当 / Doctor of Medical Science / Kyoto University / DFAM

La thermogenèse adaptative est un mécanisme de production de chaleur médié par les adipocytes bruns. En réponse au froid, ou à un stimulus adrénergique, les adipocytes blancs peuvent être convertis en adipocytes beiges lors d’un processus que l’on nomme le « beiging ». Contrairement aux adipocytes blancs, les adipocytes beiges et bruns expriment des taux élevés de la protéine de découplage 1 (UCP1) et dissipent l'énergie sous forme de chaleur grâce à l'oxydation des lipides. Il a été démontré chez les rongeurs que l’activation des adipocytes bruns et beiges entraîne une réduction significative du poids corporel et l’activation de ces adipocytes chez l’humain semble être un traitement prometteur contre l’obésité et le diabète. Nous avons précédemment identifié un rôle essentiel de la protéine d’échafaudage 14-3-3ζ dans l'adipogenèse, mais son rôle dans d'autres processus adipocytaires reste incertain. Une des premières fonctions identifiées de la 14-3-3ζ est sa capacité à réguler l'activité enzymatique de la tyrosine hydroxylase, indispensable à la production de norépinephrine pour la thermogenèse. Notre étude vise donc à déterminer si la 14-3-3ζ influence le développement et la fonction des adipocytes beiges et bruns. Nos données montrent que la délétion d’un allèle du gène de la 14-3-3ζ n’affecte pas la tolérance au froid aiguë. Comparées aux souris de type sauvage (WT), les souris transgéniques mâles surexprimant la 14-3-3ζ (TAP) ont une meilleure tolérance au froid aiguë (3 heures, 4 °C) et chronique (3 jours, 4 °C). On observe chez les TAP une augmentation du beiging due à une élévation significative de l'ARNm et de la protéine UCP1 dans le tissu adipeux blanc inguinal (iWAT). Par ailleurs, les souris TAP présentent également une réduction significative de la conductance thermique lors d’exposition au froid leur permettant de mieux conserver la chaleur. Collectivement, nos résultats soulignent le rôle novateur de la 14-3-3ζ dans le beiging et nous permettent de mieux comprendre comment la thermogenèse adaptative est régulée. / Adaptive thermogenesis is a mechanism of heat production primarily mediated by brown fat. In some instances, cold exposure or adrenergic stimuli can convert white adipocytes into brown-like or beige adipocytes during a process termed “beiging”. Both beige and brown adipocytes express higher levels of uncoupling protein 1 (UCP1) and can release energy in the form of heat following lipid oxidation. The activation of these thermogenic adipocytes increases energy expenditure to reduce body weight in rodents, and it has been postulated to be a promising therapy for the treatment of obesity and diabetes. We previously identified an essential role of the molecular scaffold, 14-3-3ζ, in adipogenesis, but its roles in other adipocyte processes is uncertain. An early identified function of 14-3-3 was its ability to regulate the enzymatic activity of tyrosine hydroxylase, which is indispensable in the production of norepinephrine for thermogenesis. Thus, our study aims to investigate whether 14-3-3ζ influences the development and function of beige and brown adipocytes. We report here that one allele deletion of the gene of 14-3-3ζ did not affect acute cold tolerance. On the other hand, transgenic overexpression of 14-3-3ζ in male mice (TAP) improves cold tolerance due to enhanced beiging with a remarkable increase in Ucp1 mRNA and protein in inguinal white adipose tissue (iWAT). Interestingly, beiging is increased in the TAP mice without any changes in sensitivity to beta-adrenergic stimuli, sympathetic innervation, or norepinephrine content being detected between WT and TAP mice. TAP mice also displayed significantly lower thermal conductance decreasing heat loss during the chronic cold challenge. Collectively, our results point to a novel role of 14-3-3ζ in beiging and increases our understanding of how adaptive thermogenesis is regulated.

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