Amygdalar Metabolic Activity Independently Associates With Progression of Visceral Adiposity

Abstract

Context: Epidemiologic data link psychological stress to adiposity. The underlying mechanisms remain uncertain.

Objectives: To test whether (i) higher activity of the amygdala, a neural center involved in the response to stress, associates with greater visceral adipose tissue (VAT) volumes and (ii) this association is mediated by increased bone marrow activity.

Setting: Massachusetts General Hospital, Boston, Massachusetts.

Patients: Two hundred forty-six patients without active oncologic, cardiovascular, or inflammatory disease who underwent clinical 18F-fluorodeoxyglucose positron emission tomography/computed tomography imaging were studied. VAT imaging was repeated ∼1 year later in 68 subjects.

Design: Metabolic activity of the amygdala (AmygA), hematopoietic tissue activity, and adiposity volumes were measured with validated methods.

Main outcome measure: The relationship between AmygA and baseline and follow-up VAT.

Results: AmygA associated with baseline body mass index (standardized β = 0.15; P = 0.01), VAT (0.19; P = 0.002), and VAT/subcutaneous adipose tissue ratio (0.20; P = 0.002), all remaining significant after adjustment for age and sex. AmygA also associated with bone marrow activity (0.15; P = 0.01), which in turn associated with VAT (0.34; P < 0.001). Furthermore, path analysis showed that 48% of the relationship between AmygA and baseline VAT was mediated by increased bone marrow activity (P = 0.007). Moreover, AmygA associated with achieved VAT after 1 year (P = 0.02) after adjusting for age, sex, and baseline VAT.

Conclusions: These results suggest a neurobiological pathway involving the amygdala and bone marrow linking psychosocial stress to adiposity in humans. Future studies should test whether targeting this mechanism attenuates adiposity and its complications.

Figure 1.

Subject selection schema. MGH, Massachusetts General Hospital.

Figure 2.

(A) Comparison of an individual with low amygdalar activity with an individual with high amygdalar activity. The arrows identify bilateral amygdalae in each subject. (B) Comparison of baseline and achieved visceral adipose tissue in an individual with lower baseline amygdalar activity with that of an individual with higher baseline amygdalar activity.

Figure 3.

Mediation model for hypothesized pathway from baseline amygdalar metabolic activity to baseline visceral adiposity. A single mediator analysis demonstrated that bone marrow activity was a significant mediator [standardized β (95% CI) = 0.06 (0.007, 0.13); P = 0.007] of the relationship between baseline AmygA and baseline VAT, accounting for 48% of the total effect. Standardized regression coefficients are shown. Analyses included age and sex as covariates. a, effect of AmygA on bone marrow activity; b, effect of bone marrow activity on VAT; c, total effect of AmygA on VAT; c’, residual direct effect of AmygA on VAT (independent of mediated effects).

Figure 4.

Proposed mechanism linking amygdalar activity to increased visceral adipose tissue.