Adult food choices depend on sex and exposure to early-life stress: Underlying brain circuitry, adipose tissue adaptations and metabolic responses

Children who experience severe early life stress show persistent deficits in many aspects of cognitive and social adaptation. Early stress might be associated with these broad changes in functioning because it impairs general learning mechanisms. To explore this possibility, we examined whether individuals who experienced abusive caregiving in childhood had difficulties with instrumental learning and/or cognitive flexibility as adolescents. Fifty‐three 14–17‐year‐old adolescents (31 exposed to high levels of childhood stress, 22 control) completed an fMRI task that required them to first learn associations in the environment and then update those pairings. Adolescents with histories of early life stress eventually learned to pair stimuli with both positive and negative outcomes, but did so more slowly than their peers. Furthermore, these stress‐exposed adolescents showed markedly impaired cognitive flexibility; they were less able than their peers to update those pairings when the contingencies changed. These learning problems were reflected in abnormal activity in learning‐ and attention‐related brain circuitry. Both altered patterns of learning and neural activation were associated with the severity of lifetime stress that the adolescents had experienced. Taken together, the results of this experiment suggest that basic learning processes are impaired in adolescents exposed to early life stress. These general learning mechanisms may help explain the emergence of social problems observed in these individuals.

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Mice Exposed to Early Life Stress Display Sex‐Specific Upregulation of Leptin Gene Expression in Adipose Tissue

The FASEB Journal ◽

10.1096/fasebj.2019.33.1_supplement.593.13 ◽

2019 ◽

Vol 33 (S1) ◽

Author(s):

Jacqueline Renee Leachman ◽

Matthew Rea ◽

Celia Ritter ◽

Xiu Xu ◽

Carolina Dalmasso ◽

...

Keyword(s):

Gene Expression ◽

Adipose Tissue ◽

Life Stress ◽

Early Life ◽

Early Life Stress

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Capsaicin‐Induced Stimulation of Sensory Neurons in Adipose Tissue Promotes Increases in Blood Pressure in Mice Exposed to Early Life Stress

The FASEB Journal ◽

10.1096/fasebj.2019.33.1_supplement.574.11 ◽

2019 ◽

Vol 33 (S1) ◽

Author(s):

Carolina Dalmasso ◽

Jacqueline R. Leachman ◽

Sophia Mounce ◽

Xiu Xu ◽

Analia S. Loria

Keyword(s):

Blood Pressure ◽

Adipose Tissue ◽

Sensory Neurons ◽

Life Stress ◽

Early Life ◽

Early Life Stress ◽

Stimulation Of

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Abstract 016: Sex-Specific Effects of Neuropeptide Y2 Receptor (y2) Deletion in Adipose Tissue From Mice Exposed to Early Life Stress

Hypertension ◽

10.1161/hyp.74.suppl_1.016 ◽

2019 ◽

Vol 74 (Suppl_1) ◽

Author(s):

Jacqueline R Leachman ◽

Xiu Xu ◽

Carolina Dalmasso ◽

Bradley K Taylor ◽

Analia S Loria

Keyword(s):

Adipose Tissue ◽

Life Stress ◽

Early Life ◽

Early Life Stress ◽

Specific Effects ◽

Y2 Receptor

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Abstract P197: Increased Serotonin In Visceral Adipose Tissue May Contribute To Stimulate Sensory Neurons Mediating Obesity Hypertension In Mice Exposed To Early Life Stress

Hypertension ◽

10.1161/hyp.78.suppl_1.p197 ◽

2021 ◽

Vol 78 (Suppl_1) ◽

Author(s):

Carolina Dalmasso ◽

Jacqueline Leachman ◽

Sundus Ghuneim ◽

Nermin Ahmed ◽

Jorge F Giani ◽

...

Keyword(s):

Adipose Tissue ◽

Protein Expression ◽

Sensory Neurons ◽

Life Stress ◽

Early Life ◽

Maternal Separation ◽

Tryptophan Hydroxylase ◽

Early Life Stress ◽

Trpv1 Channels ◽

Stimulation Of

Male C57BL/6J mice exposed to maternal separation and early weaning (MSEW), a mouse model of early life stress, display increased blood pressure (BP) and sympathetic activation compared to obese controls when fed a high fat diet (HF). Moreover, HF-fed MSEW males display exacerbated BP responses to the acute stimulation of the adipose afferent reflex (AAR) in epididymal white adipose tissue (eWAT). The aim of this study was to investigate the contribution of endogenous factors that could stimulate fat sensory neurons. MSEW and control (C) mice (n=8/group) were placed on a LF or HF (10% and 60% Kcal from fat, respectively) for 16 weeks. Then, serum obtained by decapitation and adipose tissue samples were collected to measure mRNA and protein expression of 15 factors and receptors known to activate sensory neurons. No differences were found across measurements on LF. Plasma AGT and AngII were decreased in HF-fed MSEW compared to C (AGT: 760±48 vs. 1267±161 ng/ml, p<0.05; AngII; 413±57 vs. 1082±340 pmol/l, p<0.07, Attoquant) and no differences were found in leptin (103±6 vs. 104±4 ng/ml, p<0.87). In eWAT, MSEW and C showed similar AGT (2.1±0.4 vs. 1.9±0.3 ng/ml per g tissue), AngII (1.7±0.2 vs. 2.3±0.5 pg AngII/mg tissue), ACE 1 activity (21.5±1.2 vs. 20.0±0.9 RFU/min/μg protein, p<0.33) and leptin (102.8±6.1 vs. 104.5±6.8 ng/mg of tissue, p<0.87). However, HF-fed MSEW showed increased eWAT mRNA expression of tryptophan hydroxylase 1 (Tph1), the rate limiting enzyme in serotonin (5-HT) synthesis (10.2±2.9 vs. 1.6±0.3 2 -ΔΔct , p<0.03). SERT-Tph1-MAO signaling pathway protein expression was activated, and fat serotonin concentration was also increased in eWAT from obese MSEW mice compared to C (16.58±1.5 vs. 8.5±2.1 ug/mg of tissue, p<0.01). Acute stimulation of eWAT with serotonin (10-6 M, 4 sites, 2 ul/site) tend to increase pressor response in MSEW mice (p<0.066, n=2-3). Unlike in female MSEW mice, our study demonstrates that MSEW does not increase circulating and tissue AGT, Ang II and leptin in male mice. Taken together, these data suggest that increased local serotonin could be endogenously sensitizing the sensory neurons in obese MSEW mice contributing to chronic AAR stimulation, directly via TRPV1 channels, or indirectly, via acid-sensing ion channels.

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Epididymal Fat-Derived Sympathoexcitatory Signals Exacerbate Neurogenic Hypertension in Obese Male Mice Exposed to Early Life Stress

Hypertension ◽

10.1161/hypertensionaha.121.17298 ◽

2021 ◽

Author(s):

Carolina Dalmasso ◽

Jacqueline R. Leachman ◽

Sundus Ghuneim ◽

Nermin Ahmed ◽

Eve R. Schneider ◽

...

Keyword(s):

Adipose Tissue ◽

Mean Arterial Pressure ◽

Arterial Pressure ◽

White Adipose Tissue ◽

Life Stress ◽

Early Life ◽

Early Life Stress ◽

Male Mice ◽

Epididymal White Adipose Tissue ◽

Obese Male

Previously, we have shown that male mice exposed to maternal separation and early weaning (MSEW)—a mouse model of early life stress—display increased mean arterial pressure compared with controls when fed a high-fat diet. As the stimulation of sensory nerves from fat has been shown to trigger the adipose afferent reflex, we tested whether MSEW male mice show obesity-associated hypertension via the hyperactivation of this sympathoexcitatory mechanism. After 16 weeks on high-fat diet, MSEW mice displayed increased blood pressure, sympathetic activation, and greater depressor response to an α-adrenergic blocker when compared with controls ( P <0.05; n=8), despite no differences in adiposity and plasma leptin. The acute infusion of capsaicin in epididymal white adipose tissue (1.5 pmol/μL of capsaicin, 8 μL/per site, 4 sites, bilaterally) increased the total pressor response in MSEW mice compared with controls (110±19 versus 284±33 mm Hg×30 minutes; P <0.05; n=8). This response was associated with neuronal activation in OVLT, posterior paraventricular nucleus of the hypothalamus, and RVLM ( P <0.05 versus control; n=6–7). Renal denervation abolished both the acute and chronic elevated mean arterial pressure in obese MSEW mice. Moreover, selective sensory denervation of epididymal white adipose tissue using resiniferatoxin (10 pmol/µL solution; n=6) decreased mean arterial pressure in obese MSEW mice only ( P <0.05 versus control). Obese MSEW mice displayed increased epididymal white adipose tissue levels of both tryptophan hydroxylase (Tph1) mRNA expression and its synthesis product serotonin (8.3±1.9 versus 16.6±1.7 ug/mg tissue; P <0.05 versus control). Thus, afferent sensory signals from epididymal white adipose tissue may contribute to the exacerbated fat–brain–blood pressure axis displayed by obese male mice exposed to early life stress.

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