Obesity is a major risk factor for insulin resistance and type 2 diabetes. In adipose tissue, obesity-mediated insulin resistance correlates with the accumulation of proinflammatory macrophages and inflammation. However, the causal relationship of these events is unclear. Here, we report that obesity-induced insulin resistance in mice precedes macrophage accumulation and inflammation in adipose tissue. Using a mouse model that combines genetically induced, adipose-specific insulin resistance (mTORC2-knockout) and diet-induced obesity, we found that insulin resistance causes local accumulation of proinflammatory macrophages. Mechanistically, insulin resistance in adipocytes results in production of the chemokine monocyte chemoattractant protein 1 (MCP1), which recruits monocytes and activates proinflammatory macrophages. Finally, insulin resistance (high homeostatic model assessment of insulin resistance [HOMA-IR]) correlated with reduced insulin/mTORC2 signaling and elevated MCP1 production in visceral adipose tissue from obese human subjects. Our findings suggest that insulin resistance in adipose tissue leads to inflammation rather than vice versa.

Xylitol and erythritol are widely used in a variety of food and oral care products as sugar substitutes. Although a number of studies have been conducted on the health benefits of xylitol since the 1960s, erythritol only attracted the attention of researchers during the early 1990s. Historically, researchers mainly focused on the effects of xylitol and other sugar alcohols on oral and dental healthcare while the anti-diabetic or antihyperglycemic effects have only been revealed recently. Though a few reviews have been published on the health benefits of sugar alcohols in the last few decades, none of them closely evaluated the antihyperglycemic potential and underlying mechanisms, particularly with a focus on xylitol and erythritol. The current review thoroughly analyzes the anti-diabetic and antihyperglycemic effects as well as other metabolic effects of xylitol and erythritol using articles published in PubMed since the 1960s, containing research done on experimental animals and humans. This review will help researchers ascertain the controversies surrounding sugar alcohols, investigate further beneficial effects of them as well as aid food industries in exploring the possibilities of using sugar alcohols as anti-diabetic supplements in diabetic foods and food products.

Aim: To determine whether a dose‐dependent effect in the stimulation of gut hormone release (plasma cholecystokinin [CCK], active glucagon‐like peptide‐1 [aGLP‐1] and peptide tyrosine tyrosine [PYY]) is found for the natural sweetener erythritol. Materials and Methods: Twelve healthy, lean volunteers received solutions with 10, 25 or 50 g erythritol, or tap water enriched with ¹³ C‐sodium acetate on four study days via a nasogastric tube in this randomized (active treatments), placebo‐controlled, double‐blind, cross‐over trial. Blood samples and breath samples ( ¹³ C‐sodium acetate method for measurement of gastric emptying [GE]) were taken at regular intervals, and sensations of appetite and gastrointestinal symptoms were rated. Results: We found (a) a dose‐dependent stimulation of CCK, aGLP‐1 and PYY, and slowing of GE, (b) no effect on blood glucose, insulin, motilin, glucagon or glucose‐dependent insulinotropic polypeptide, (c) no effect on blood lipids and uric acid, and (d) no abdominal pain, nausea or vomiting. Conclusions: Solutions with 10 and 50 g of erythritol stimulated gut hormone release. Emptying of erythritol‐containing solutions from the stomach was slower compared with placebo. There was no effect on plasma glucose, insulin, glucagon, blood lipids or uric acid. All doses were well tolerated.

The natural sweeteners erythritol and xylitol might be helpful to reduce sugar consumption and therefore prevent obesity and diabetes. The aim of the present study was to determine the absorption and metabolization into erythronate of different concentrations of erythritol and xylitol. Seventeen healthy lean participants received intragastric solutions of 10, 25, or 50 g erythritol or 7, 17, or 35 g xylitol on three study days in a randomized order. The study was double blinded with respect to the doses administered. We assessed plasma concentrations of erythritol, xylitol, and erythronate at fixed time intervals after administration with gas chromatography-mass spectrometry. We found: (i) a dose-dependent and saturable absorption of erythritol, (ii) a very low absorption of xylitol, (iii) a dose-dependent metabolization of erythritol into erythronate, and (iv) no metabolization of xylitol into erythronate. The implications of the metabolization of erythritol into erythronate for human health remain to be determined and more research in this area is needed.

Glucose induces the release of gastrointestinal (GI) satiation hormones, such as glucagon-like peptide 1 (GLP-1) and peptide tyrosine tyrosine (PYY), in part via the activation of the gut sweet taste receptor (T1R2/T1R3). The primary objective was to investigate the importance of T1R2/T1R3 for the release of cholecystokinin (CCK), GLP-1, and PYY in response to D-allulose and erythritol by assessing the effect of the T1R2/T1R3 antagonist lactisole on these responses and as secondary objectives to study the effect of the T1R2/T1R3 blockade on gastric emptying, appetite-related sensations, and GI symptoms. In this randomized, controlled, double-blind, crossover study, 18 participants (5 men) with a mean ± SD BMI (in kg/m²) of 21.9 ± 1.7 and aged 24 ± 4 y received an intragastric administration of 25 g D-allulose, 50 g erythritol, or tap water, with or without 450 parts per million (ppm) lactisole, respectively, in 6 different sessions. ¹³C-sodium acetate was added to all solutions to determine gastric emptying. At fixed time intervals, blood and breath samples were collected, and appetite-related sensations and GI symptoms were assessed. Data were analyzed with linear mixed-model analysis. D-allulose and erythritol induced a significant release of CCK, GLP-1, and PYY compared with tap water (all P_Holm < 0.0001, d_z >1). Lactisole did not affect the D-allulose– and erythritol-induced release of CCK, GLP-1, and PYY (all P_Holm > 0.1). Erythritol significantly delayed gastric emptying, increased fullness, and decreased prospective food consumption compared with tap water (P_Holm = 0.0002, d_z = –1.05; P_Holm = 0.0190, d_z = 0.69; and P_Holm = 0.0442, d_z = –0.62, respectively). D-allulose and erythritol stimulate the secretion of GI satiation hormones in humans. Lactisole had no effect on CCK, GLP-1, and PYY release, indicating that D-allulose– and erythritol-induced GI satiation hormone release is not mediated via T1R2/T1R3 in the gut.

Background Morbid obesity is a worldwide epidemic and is increasingly treated by bariatric surgery. Fatty liver is a common finding; almost half of all patients with non-alcoholic steatohepatitis develop steatohepatitis. Bariatric surgery improves steatohepatitis documented by liver biopsy and single voxel magnetic resonance imaging (MRI) techniques. Objective To investigate changes before and after bariatric surgery using whole organ MRI quantification of liver, visceral, and subcutaneous fat. Setting University of Basel Hospital and St. Clara Research Ltd, Basel, Switzerland. Methods Sixteen morbidly obese patients were evaluated by abdominal MRI-scanning before and 3, 6, 12, and 24 months after bariatric surgery to measure percentage liver fat (%-LF), total liver volume (TLV) and visceral and subcutaneous adipose tissues (VAT and SAT). Fasting plasma samples were taken for measurement of glucose, insulin, blood lipids, and liver biomarkers. In a control group of 12 healthy lean volunteers, the liver biomarker was also measured. Results The reproducibility of fat quantification by use of MRI was excellent. LF decreased significantly faster than VAT and SAT (%-LF vs. VAT p < 0.001 and %-LF vs. SAT p < 0.001). At certain time points, %-LF, VAT, and SAT were associated with changes in blood lipids and insulin. Conclusions MRI quantification offers excellently reproducible results in measurement of liver fat and visceral and subcutaneous adipose tissues. Liver fat decreased significantly faster than visceral or subcutaneous adipose tissue. Decrease in %-LF and VAT is associated with decrease in total cholesterol, LDL, and plasma insulin.