Effects of intragastric administration of L-tryptophan on the glycaemic response to a nutrient drink in men with type 2 diabetes - impacts on gastric emptying, glucoregulatory hormones and glucose absorption

Published: 05 January 2021BACKGROUND: The rate of gastric emptying and glucoregulatory hormones are key determinants of postprandial glycaemia. Intragastric administration of L-tryptophan slows gastric emptying and reduces the glycaemic response to a nutrient drink in lean individuals and those with obesity. We investigated whether tryptophan decreases postprandial glycaemia and slows gastric emptying in type 2 diabetes (T2D). METHODS: Twelve men with T2D (age: 63 ± 2 years, HbA1c: 49.7 ± 2.5 mmol/mol, BMI: 30 ± 1 kg/m2) received, on three separate occasions, 3 g ('Trp-3') or 1.5 g ('Trp-1.5') tryptophan, or control (0.9% saline), intragastrically, in randomised, double-blind fashion, 30 min before a mixed-nutrient drink (500 kcal, 74 g carbohydrates), containing 3 g 3-O-methyl-D-glucose (3-OMG) to assess glucose absorption. Venous blood samples were obtained at baseline, after tryptophan, and for 2 h post-drink for measurements of plasma glucose, C-peptide, glucagon and 3-OMG. Gastric emptying of the drink was quantified using two-dimensional ultrasound. RESULTS: Tryptophan alone stimulated C-peptide (P = 0.002) and glucagon (P = 0.04), but did not affect fasting glucose. In response to the drink, Trp-3 lowered plasma glucose from t = 15-30 min and from t = 30-45 min compared with control and Trp-1.5, respectively (both P < 0.05), with no differences in peak glucose between treatments. Gastric emptying tended to be slower after Trp-3, but not Trp-1.5, than control (P = 0.06). Plasma C-peptide, glucagon and 3-OMG increased on all days, with no major differences between treatments. CONCLUSIONS: In people with T2D, intragastric administration of 3 g tryptophan modestly slows gastric emptying, associated with a delayed rise, but not an overall lowering of, postprandial glucose.Maryam Hajishafiee, Rachel A. Elovaris, Karen L. Jones, Leonie K. Heilbronn, Michael Horowitz, Sally D. Poppitt and Christine Feinle-Bisse

Obesity, inflammation, and insulin resistance

White adipose tissue (WAT) is considered an endocrine organ. When present in excess, WAT can influence metabolism via biologically active molecules. Following unregulated production of such molecules, adipose tissue dysfunction results, contributing to complications associated with obesity. Previous studies have implicated pro- and anti-inflammatory substances in the regulation of inflammatory response and in the development of insulin resistance. In obese individuals, pro-inflammatory molecules produced by adipose tissue contribute to the development of insulin resistance and increased risk of cardiovascular disease. On the other hand, the molecules with anti-inflammatory action, that have been associated with the improvement of insulin sensitivity, have your decreased production. Imbalance of these substances contributes significantly to metabolic disorders found in obese individuals. The current review aims to provide updated information regarding the activity of biomolecules produced by WAT

The health outcomes of human offspring conceived by assisted reproductive technologies (ART)

Themed Issue: Assisted Reproductive Treatments (ART) and DOHADConcerns have been raised about the health and development of children conceived by assisted reproductive technologies (ART) since 1978. Controversially, ART has been linked with adverse obstetric and perinatal outcomes, an increased risk of birth defects, cancers, and growth and development disorders. Emerging evidence suggests that ART treatment may also predispose individuals to an increased risk of chronic ageing related diseases such as obesity, type 2 diabetes and cardiovascular disease. This review will summarize the available evidence on the short-term and long-term health outcomes of ART singletons, as multiple pregnancies after multiple embryos transfer, are associated with low birth weight and preterm delivery, which can separately increase risk of adverse postnatal outcomes, and impact long-term health. We will also examine the potential factors that may contribute to these health risks, and discuss underlying mechanisms, including epigenetic changes that may occur during the preimplantation period and reprogram development in utero, and adult health, later in life. Lastly, this review will consider the future directions with the view to optimize the long-term health of ART children.M. Chen and L. K. Heilbron

Intermittent fasting: what questions should we be asking?

Obesity and overweight are contributing factors to chronic disease. Lifestyle management, which incorporates advice on moderate daily caloric restriction (CR) and physical activity to reduce body weight, is the cornerstone treatment in practice. Intermittent fasting (IF) is a popular alternative that cycles fasting with unrestricted eating periods. IF appears to be an equivalent approach to CR to induce weight loss, although as yet there is limited long-term evidence. Some controversy exists as to whether IF yields superior health benefits to CR. Discrepancies between studies may be due to the heterogeneity in the design of IF protocols. There is also still some concerns around the safety and feasibility of IF compared to CR, which has not been well-studied to date. Moreover, the underlying cellular pathways that are differentially activated in IF in comparison to CR requires further investigation in humans. This review summarises trials that have compared IF with CR, and discusses evidence from animal studies to raise questions for future research in humans.Kai Liu, Bo Liu, Leonie K. Heilbron

Intermittent feeding and circadian rhythm in critical illness

Purpose of review: Circadian rhythms, i.e., periodic oscillations in internal biological processes, modulate metabolic processes such as hormonal signalling, nutrient absorption, and xenobiotic detoxification. Meal timing is a strong entraining cue for peripheral clocks in various organs, and eating out of circadian phases can impair glucose, gastrointestinal, and muscle metabolism. Sleep/wake cycles and circadian rhythms are extremely disrupted during critical illness. Timing of nutritional support may help preserve circadian rhythms and improve post-Intensive Care Unit (ICU) recovery. This review summarises circadian disruptors during ICU admission and evaluates the potential benefits of intermittent feeding on metabolism and circadian rhythms. Recent findings: Rhythmic expression of core clock genes becomes rapidly disturbed during critical illness and remains disturbed for weeks. Intermittent, bolus, and cyclic enteral feeding have been directly compared to routine continuous feeding, yet no benefits on glycaemic control, gastrointestinal tolerance, and muscle mass have been observed and impacts of circadian clocks remain untested. Summary: Aligning timing of nutritional intake, physical activity, and/or medication with circadian rhythms are potential strategies to reset peripheral circadian rhythms and may enhance ICU recovery but is not proven beneficial yet. Therefore, selecting intermittent feeding over continuous feeding must be balanced against the pros and cons of clinical practice.Imre W.K. Kouw, Leonie K. Heilbronn, and Arthur R.H. van Zante

Intermittent fasting increases energy expenditure and promotes adipose tissue browning in mice

Objective: Intermittent fasting (IF) may limit metabolic adaptations that reduce energy expenditure, potentially by stimulating white adipose tissue (WAT) browning. The aim of this study was to examine the effects of 8 wk of IF on energy metabolism and markers of WAT browning in lean and diet-induced obese mice and in women who were overweight or obese. Methods: Male C57 BL/6 J mice were fed chow or a high-fat diet (HFD; 43%) for 8 wk before undergoing IF (3 non-consecutive d/wk) for an additional 8 wk. Food intake, energy expenditure, and inguinal and gonadal fat pads were collected in fed or fasted conditions (22 h, IF mice only). Subcutaneous adipose tissue (SAT) was also collected at baseline, and after 8 wk of IF (in the fed state, and after a 24-h fast), in women with overweight or obesity. Uncoupling protein 1 (UCP1) was assessed by quantitative real-time polymerase chain reaction (mice and humans) and immunohistochemistry (mice). Results: IF reduced body weight and energy intake in HFD fed mice and reduced gonadal and inguinal fat pad weights in both diet groups. IF increased energy expenditure, meal number, Ucp1 mRNA levels in inguinal and gonadal fat depots, and UCP1 protein in inguinal fat in both diet groups on fed days. In women, IF reduced body weight and fat mass, but did not alter UCP1mRNA levels. Conclusions: IF increased energy expenditure and promoted WAT browning in mice but did not alter UCP1 mRNA levels in SAT in women.Bo Liu, Amanda J. Page, Amy T. Hutchison, Gary A. Wittert, Leonie K. Heilbron

Distinct adult metabolic consequences following ovarian stimulation versus in vitro culture of mouse embryos

Session abstract: O-307 Tuesday, October 15, 2013 05:30 PMM. Chen, L. Wu, G.A. Wittert, R.J. Norman, R.L. Robker, L.K. Heilbron

Effects of intermittent fasting or calorie restriction on markers of lipid metabolism in human skeletal muscle

Context: Impaired lipid metabolism is linked with obesity-associated insulin resistance, which may be reversed by caloric restriction (CR). Objective: In a secondary analysis of a randomized controlled trial, we compared the effects of intermittent fasting (IF) and CR on markers of lipid metabolism in muscle. Design: Seventy-six women (BMI 25-40 kg/m²) were randomized to one of three diets for eight weeks and provided with foods at 70% (CR70 and IF70) or 100% (IF100) of energy requirements. IF groups ate breakfast, prior to a 24-hour fast on 3 non-consecutive days per week. On non-fasting days, IF70 ate at 100% and IF100 ate at 145% of energy requirements to achieve the prescribed target. Weight, body composition, insulin sensitivity by clamp, non-esterified fatty acids (NEFA), β-hydroxybutyrate, and markers of lipid metabolism and oxidative stress in muscle by qPCR were measured at baseline and week 8 following a 12-hour overnight fast (all groups) and 24-hour fast (IF groups). Results: IF70 resulted in greater weight and fat losses and reduced NEFA versus CR70 and IF100 after an overnight fast. IF70 and IF100 induced a greater reduction only in mRNA levels of antioxidant enzymes GPX1, SOD1 and SOD2 versus CR70. Fasting for 24-hours increased NEFA and β-hydroxybutyrate in IF groups, but impaired insulin sensitivity and increased PLIN5 mRNA levels. Conclusoins: In comparison to CR, IF did not increase markers of lipid metabolism in muscle, but reduced expression of antioxidant enzymes. However, fasting-induced insulin resistance was detected, alongside increased PLIN5 expression, potentially reflecting transient lipid storage.Bo Liu, Amy T. Hutchison, Campbell H. Thompson, Kylie Lange, Gary A. Wittert, and Leonie K. Heilbron

Intermittent fasting increases growth differentiation factor 15 in females with overweight or obesity but not associated with food intake

Available online 9 December 2022Growth differentiation factor 15 (GDF15) increases with acute fast in animals, and high GDF15 reduces food intake in rodents. We explored whether GDF15 was altered following intermittent fasting (IF) versus caloric restriction (CR), and associations with energy intake. Females with obesity received all foods at 70% (IF70 and CR70) or 100% of energy requirements for 8 weeks. IF ate 2–9% less than provided on refeeding days, resulting in greater weight losses. GDF15 was increased 5% more in IF70 versus CR70, but not associated with energy intake. This rise in GDF15 is unlikely to explain restriction of energy intake during IF.Kai Liu, Bo Liu, Gary A. Wittert, Campbell H. Thompson, Amy T. Hutchison, Leonie K. Heilbron

Intermittent fasting improves glucose tolerance and promotes adipose tissue remodeling in male mice fed a high-fat diet

Obesity is associated with increased macrophage and extracellular matrix accumulation in adipose tissue, which can be partially reversed following weight loss by daily caloric restriction. This study examined the effects of 8 weeks of intermittent fasting (IF; 24-hour fast on 3 nonconsecutive days per week) in mice fed a chow or high-fat diet (HFD; 43% fat) on markers of adipose tissue inflammation and fibrosis. We found that IF decreased energy intake, body weight, and fat cell size in HFD-fed mice and decreased fat mass and improved glucose tolerance in chow- and HFD-fed mice. IF decreased mRNA levels of macrophage markers (Lgals3, Itgax, Ccl2, and Ccl3) in inguinal and gonadal fat, as well as adipose tissue macrophage numbers in HFD-fed mice only, and altered genes involved in NLRP3 inflammasome pathway in both diet groups. IF increased mRNA levels of matrix metallopeptidase 9, which is involved in extracellular matrix degradation, and reduced mRNA levels of collagen 6 α-1 and tissue inhibitor of matrix metallopeptidase 1, as well as fibrosis in gonadal fat in HFD-fed mice. In summary, our results show that intermittent fasting improved glucose tolerance in chow- and HFD-fed mice and ameliorated adipose tissue inflammation and fibrosis in HFD-fed mice.Bo Liu, Amanda J. Page, George Hatzinikolas, Miaoxin Chen, Gary A. Wittert and Leonie K. Heilbron