Posterior cervical brown fat and CXCL14 levels in the first year of life: sex differences and association with adiposity

Context: Brown adipose tissue (BAT) is particularly abundant in neonates but its association with measures of adiposity and metabolic health in early infancy is poorly delineated. Besides sustaining non-shivering thermogenesis, BAT secretes brown adipokines that act on systemic metabolism. The chemokine CXCL14 has been identified as a brown adipokine in experimental studies.

Objective: To determine the relationships among BAT activity, adiposity and circulating CXCL14 levels in the first year of life in girls and boys.

Design, setting and participants: Indices of fat accretion, circulating endocrine-metabolic parameters and serum CXCL14 levels were assessed longitudinally in a cohort of infants at birth and at 4 and 12 months. BAT activity was estimated using infrared thermography only at age 12 months.

Main outcome measures: Weight and length Z-scores, total and abdominal fat content (by DXA), BAT activity at the posterior-cervical and supraclavicular regions, serum levels of glucose, insulin, insulin-like growth factor-I, high-molecular-weight adiponectin and CXCL14; CXCL14 transcript levels in neonatal BAT and liver.

Results: Posterior-cervical BAT was more active in girls than in boys (p=0.02). BAT activity was negatively associated with adiposity parameters only in girls. CXCL14 levels were higher in girls than in boys at age 12 months and correlated positively with the area of active posterior-cervical BAT in girls. Neonatal BAT showed high CXCL14 gene expression levels.

Conclusions: BAT activity and the levels of CXCL14 -a potential surrogate of BAT activity- are sex-specific in the first year of life. BAT activity associates negatively with indices of adiposity only in girls.

Methods
Here, we assessed for the first time brown adipose tissue (BAT) activity and the circulating levels of CXCL14 in a longitudinal cohort of infants in the first year of life, and determined their relationship with measures of adiposity (by DXA) and endocrine-metabolic parameters. The study cohort was composed of N= 43 infants (23 girls, 20 boys) who were recruited prenatally during the customary third-trimester visit among pregnant mothers consecutively seen in the outpatient clinics of Hospital Sant Joan de Déu and Hospital de Sant Boi – Parc Sanitari Sant Joan de Déu (Barcelona, Spain).

背景：棕色脂肪组织（brown adipose tissue, BAT）在新生儿体内含量尤为丰富，但目前学界对其与婴儿早期体脂指标及代谢健康的关联尚不明晰。除维持非战栗产热外，棕色脂肪组织还可分泌棕色脂肪因子，作用于全身代谢过程。现有实验研究已证实趋化因子CXCL14属于棕色脂肪因子。
研究目标：明确男女婴幼儿出生后第一年内，棕色脂肪组织活性、体脂水平与循环CXCL14浓度三者间的关联。
设计、研究场景与研究对象：本研究对某队列婴儿在出生时、出生后4个月及12个月时的体脂累积指标、循环内分泌代谢参数及血清CXCL14水平进行了纵向评估。仅在婴儿12月龄时，采用红外热成像技术估算其棕色脂肪组织活性。
主要结局指标：体重与身长Z评分、全身及腹部脂肪含量（双能X线吸收法，DXA）、颈后与锁骨上区域的棕色脂肪组织活性、血清葡萄糖、胰岛素、胰岛素样生长因子-I、高分子量脂联素及CXCL14水平；新生儿棕色脂肪组织与肝脏中CXCL14的转录水平。
研究结果：女婴的颈后棕色脂肪组织活性显著高于男婴（p=0.02）。仅在女婴群体中，棕色脂肪组织活性与体脂指标呈负相关。12月龄时，女婴的循环CXCL14水平显著高于男婴，且其活性颈后棕色脂肪组织面积与CXCL14水平呈正相关。新生儿棕色脂肪组织中CXCL14基因的表达水平较高。
研究结论：出生后第一年内，棕色脂肪组织活性与CXCL14水平——后者是潜在的棕色脂肪组织活性替代标志物——存在性别特异性差异。仅在女婴群体中，棕色脂肪组织活性与体脂指标呈负相关。
研究方法：本研究首次对出生后第一年的纵向队列婴幼儿的棕色脂肪组织活性与循环CXCL14水平进行了检测，并明确了二者与体脂指标（双能X线吸收法，DXA检测）及内分泌代谢参数的关联。本研究队列共纳入43名婴幼儿（女婴23名，男婴20名），均于产前常规孕晚期随访阶段招募，招募对象为在西班牙巴塞罗那Sant Joan de Déu医院与Sant Boi医院–Parc Sanitari Sant Joan de Déu门诊连续就诊的孕妇所诞下的婴儿。