Increased Salt Intake Decreases Diet-Induced Thermogenesis in Healthy Volunteers: A Randomized Placebo-Controlled Study

High salt intake ranks among the most important risk factors for noncommunicable diseases. Western diets, which are typically high in salt, are associated with a high prevalence of obesity. High salt is thought to be a potential risk factor for obesity independent of energy intake, although the underlying mechanisms are insufficiently understood. A high salt diet could influence energy expenditure (EE), specifically diet-induced thermogenesis (DIT), which accounts for about 10% of total EE. We aimed to investigate the influence of high salt on DIT. In a randomized, double-blind, placebo-controlled, parallel-group study, 40 healthy subjects received either 6 g/d salt (NaCl) or placebo in capsules over 2 weeks. Before and after the intervention, resting EE, DIT, body composition, food intake, 24 h urine analysis, and blood pressure were obtained. EE was measured by indirect calorimetry after a 12 h overnight fast and a standardized 440 kcal meal. Thirty-eight subjects completed the study. Salt intake from foods was 6 g/d in both groups, resulting in a total salt intake of 12 g/d in the salt group and 6 g/d in the placebo group. Urine sodium increased by 2.29 g/d (p < 0.0001) in the salt group, indicating overall compliance. The change in DIT differed significantly between groups (placebo vs. salt, p = 0.023). DIT decreased by 1.3% in the salt group (p = 0.048), but increased by 0.6% in the placebo group (NS). Substrate oxidation indicated by respiratory exchange ratio, body composition, resting blood pressure, fluid intake, hydration, and urine volume did not change significantly in either group. A moderate short-term increase in salt intake decreased DIT after a standardized meal. This effect could at least partially contribute to the observed weight gain in populations consuming a Western diet high in salt.

Targeting PLD2 in adipocytes augments adaptive thermogenesis by improving mitochondrial quality and quantity in mice

Phospholipase D (PLD)2 via its enzymatic activity regulates cell proliferation and migration and thus is implicated in cancer. However, the role of PLD2 in obesity and type 2 diabetes has not previously been investigated. Here, we show that during diet-induced thermogenesis and obesity, levels of PLD2 but not PLD1 in adipose tissue are inversely related with uncoupling protein 1, a key thermogenic protein. We demonstrate that the thermogenic program in adipose tissue is significantly augmented in mice with adipocyte-specific Pld2 deletion or treated with a PLD2-specific inhibitor and that these mice are resistant to high fat diet–induced obesity, glucose intolerance, and insulin resistance. Mechanistically, we show that Pld2 deletion in adipose tissue or PLD2 pharmacoinhibition acts via p62 to improve mitochondrial quality and quantity in adipocytes. Thus, PLD2 inhibition is an attractive therapeutic approach for obesity and type 2 diabetes by resolving defects in diet-induced thermogenesis.

Chewing increases postprandial diet-induced thermogenesis

Slow eating, which involves chewing food slowly and thoroughly, is an effective strategy for controlling appetite in order to avoid being overweight or obese. Slow eating also has the effect of increasing postprandial energy expenditure (diet-induced thermogenesis). It is still unclear whether this is due to oral stimuli; that is, the duration of tasting food in the mouth and the duration of chewing. To investigate the effects of oral stimuli on diet-induced thermogenesis in 11 healthy normal weight males, we conducted a randomized crossover study comprising three trials: (1) drinking liquid food normally, (2) drinking liquid food after tasting, and (3) adding chewing while tasting. Oral stimuli (i.e., the duration of tasting liquid food in the mouth and the duration of chewing) significantly increased diet-induced thermogenesis after drinking liquid food. This result demonstrates that the increase in diet-induced thermogenesis is due to oral stimuli rather than the influence of the food bolus. Increased diet-induced thermogenesis induced by chewing and taste stimuli may help to prevent overweight and obesity.

Epigenetic interaction between UTX and DNMT1 regulates diet-induced myogenic remodeling in brown fat

Brown adipocytes share the same developmental origin with skeletal muscle. Here we find that a brown adipocyte-to-myocyte remodeling also exists in mature brown adipocytes, and is induced by prolonged high fat diet (HFD) feeding, leading to brown fat dysfunction. This process is regulated by the interaction of epigenetic pathways involving histone and DNA methylation. In mature brown adipocytes, the histone demethylase UTX maintains persistent demethylation of the repressive mark H3K27me3 at Prdm16 promoter, leading to high Prdm16 expression. PRDM16 then recruits DNA methyltransferase DNMT1 to Myod1 promoter, causing Myod1 promoter hypermethylation and suppressing its expression. The interaction between PRDM16 and DNMT1 coordinately serves to maintain brown adipocyte identity while repressing myogenic remodeling in mature brown adipocytes, thus promoting their active brown adipocyte thermogenic function. Suppressing this interaction by HFD feeding induces brown adipocyte-to-myocyte remodeling, which limits brown adipocyte thermogenic capacity and compromises diet-induced thermogenesis, leading to the development of obesity.

The pesticide chlorpyrifos promotes obesity by inhibiting diet-induced thermogenesis in brown adipose tissue

Obesity results from a caloric imbalance between energy intake, absorption and expenditure. In both rodents and humans, diet-induced thermogenesis contributes to energy expenditure and involves the activation of brown adipose tissue (BAT). We hypothesize that environmental toxicants commonly used as food additives or pesticides might reduce BAT thermogenesis through suppression of uncoupling protein 1 (UCP1) and this may contribute to the development of obesity. Using a step-wise screening approach, we discover that the organophosphate insecticide chlorpyrifos suppresses UCP1 and mitochondrial respiration in BAT at concentrations as low as 1 pM. In mice housed at thermoneutrality and fed a high-fat diet, chlorpyrifos impairs BAT mitochondrial function and diet-induced thermogenesis, promoting greater obesity, non-alcoholic fatty liver disease (NAFLD) and insulin resistance. This is associated with reductions in cAMP; activation of p38MAPK and AMPK; protein kinases critical for maintaining UCP1 and mitophagy, respectively in BAT. These data indicate that the commonly used pesticide chlorpyrifos, suppresses diet-induced thermogenesis and the activation of BAT, suggesting its use may contribute to the obesity epidemic.

Residual thermic effects of diet induced thermogenesis (RDIT) in aging lean and obese LA/Ntu1//-cp (corpulent) rats

Diet induced thermogenesis has been proposed to account for up to 15% of the caloric content of an ingested meal and to become decreased with aging and in obesity. Genetically obese rodents have been shown to exhibit impairments in the thermic responses to diet and environment, which may partially account for an improved caloric efficiency and to contribute to their increased propensity to become obese. In the present study we sought to determine the thermic responses to diet and environment in aging obese rats when young, middle aged, and aged. Resting oxygen consumption tended to decrease with advancing age and the thermic responses were lower than predicted in obese than in lean rats. This study provides important new insights regarding the thermogenic effects of diet and diet induced thermogenesis and their potential contributions to mechanisms of energy balance across the spectrum of aging in lean and obese LA/Ntul//-cp rats

Hibiscus sabdariffa tea affects diet-induced thermogenesis and subjective satiety responses in healthy men, but not in women: a randomized crossover trial

The aim of this study was to investigate the effect of Hibiscus sabdariffa tea on energy expenditure, satiety response and food intake. This is an open-label, crossover, randomized clinical trial (RBR-5HZ86T), including 21 subjects (11 women, 10 men). The individuals were evaluated at acute moments (fasting and after eating standardized breakfast accompanied by water or Hibiscus sabdariffa tea). Resting energy expenditure was measured by indirect calorimetry, subjective satiety responses were evaluated with a visual analogue scale and food intake was assessed by using food records. The volunteers who drank the Hibiscus sabdariffa tea had lower perception of hunger (p=0.002) and greater feeling of satiety (p=0.010) and fullness (p=0.009) compared to control. Men who ingested the Hibiscus sabdariffa tea had an increase in nitrogen energy expenditure (water: 1501±290.7kcal, Hibiscus sabdariffa tea: 1619±288.9kcal; p=0.029). In comparison to control, men presented less perception of hunger (p=0.003) and desire to eat (p=0.016), increased satiety (p=0.021) and fullness (p=0.010), and women oxidized more fat (p=0.034) when they drank Hibiscus sabdariffa tea. There was no difference between treatments regarding the energy and macronutrient intake from the first meal and throughout the day (p>0.050) for all participants. The Hibiscus sabdariffa tea only affected energy expenditure and satiety responses in men. Clinical trial registry: ReBEC Platform of the Brazilian Clinical Trials Registry - RBR-5HZ86T Novelty bullets • Hibiscus sabdariffa tea promoted an increase in energy expenditure and caused less perception of hunger/desire to eat in men. • Hibiscus sabdariffa tea intake increased postprandial fat oxidation in women.

Diurnal variations of brown fat thermogenesis and fat oxidation in humans

Background/objectives Disturbed circadian rhythm is associated with an increased risk of obesity and metabolic disorders. Brown adipose tissue (BAT) is a site of nonshivering thermogenesis (NST) and plays a role in regulating whole-body energy expenditure (EE), substrate metabolism, and body fatness. In this study, we examined diurnal variations of NST in healthy humans by focusing on their relation to BAT activity. Methods Forty-four healthy men underwent 18F-fluoro-2-deoxy-D-glucose positron emission tomography and were divided into Low-BAT and High-BAT groups. In STUDY 1, EE, diet-induced thermogenesis (DIT), and fat oxidation (FO) were measured using a whole-room indirect calorimeter at 27 °C. In STUDY 2, EE, FO, and skin temperature in the region close to BAT depots (Tscv) and in the control region (Tc) were measured at 27 °C and after 90 min cold exposure at 19 °C in the morning and in the evening. Results In STUDY 1, DIT and FO after breakfast was higher in the High-BAT group than in the Low-BAT group (P < 0.05), whereas those after dinner were comparable in the two groups. FO in the High-BAT group was higher after breakfast than after dinner (P < 0.01). In STUDY 2, cold-induced increases in EE (CIT), FO, and Tscv relative to Tc in the morning were higher in the High-BAT group than in the Low-BAT group (P < 0.05), whereas those after dinner were comparable in the two groups. CIT in the High-BAT group tended to be higher in the morning than in the evening (P = 0.056). Conclusion BAT-associated NST and FO were evident in the morning, but not in the evening, suggesting that the activity of human BAT is higher in the morning than in the evening, and thus may be involved in the association of an eating habit of breakfast skipping with obesity and related metabolic disorders.