The effect of nitrate on brown fat fraction and activation in people with type 2 diabetes: a randomised, double-blind, placebo-controlled crossover trial

Abstract

Type 2 diabetes mellitus (T2DM) is a metabolic disease characterised by chronic hyperglycaemia, whereas obesity is a major risk factor which increases morbidity and mortality. Treatments that alter white adipose tissue to express a metabolically active brown adipose phenotype in rats may offer adjunct treatment in people with T2DM. To investigate whether inorganic nitrate supplementation from beetroot juice (BJ) alters brown adipose tissue (BAT) fat fraction and activation in humans. Thirteen older adults with T2DM (glycated haemoglobin [HbA1c]: 58 ± 13 mmol·mol−1 and body mass index: 29.1 ± 3.1 kg·m−2) completed a double-blind, randomised, balanced and placebo-controlled crossover study. Outcome measures (including BAT fat fraction; activation; plasma [nitrate] and [nitrite]) were assessed before and after 14-day of 140 mL·day−1 BJ containing inorganic nitrate (∼12.4 mmol·L1) or a placebo (∼0.1 mmol·L1). Magnetic resonance imaging (MRI) and infrared thermography (IRT) were performed to image supraclavicular BAT following a rested cooling protocol, consisting of 60-min exposure via a cold water (8.1 ± 1.2°C) perfused jacket. Respiratory parameters, including respiratory exchange ratio [RER] and mean skin temperature, were measured during the cooling protocol to confirm participants were not shivering. BJ significantly increased venous plasma [nitrate] and [nitrite] versus placebo (p < 0.001) but did not affect BAT fat fraction (p = 0.650) or activation (p = 0.152). Cooling significantly reduced mean skin temperature in BJ (−0.8 ± 0.7°C) and placebo (−0.6 ± 0.6°C) (p < 0.001) and RER remained representative of nonshivering thermogenesis throughout (0.88 ± 0.05 a.u.). 14-day of nitrate supplementation did not increase BAT fat fraction or activation in older adults with T2DM.

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ORCID for Zoe L. Saynor: orcid.org/0000-0003-0674-8477

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