André C Carpentier

Université de Sherbrooke | UdeS · Department of Medicine, Université de Sherbrooke

White and brown adipose tissues (WAT and BAT) regulate fatty acid metabolism and control lipid fluxes to other organs. Dysfunction of these key metabolic processes contributes to organ insulin resistance and inflammation leading to chronic diseases such as type 2 diabetes (T2D), metabolic dysfunction-associated steatohepatitis (MASH), and cardiovas...

Adipocyte hypertrophy is associated with metabolic complications independent of obesity. We aimed to determine: 1) the association between adipocyte size and postprandial fatty acid metabolism; 2) the potential mechanisms driving the obesity-independent, hypertrophy-associated dysmetabolism in vivo and at a single-cell resolution. Tracers with posi...

Background The heart relies heavily on external fatty acid (FA) for energy production. VEGFB (vascular endothelial growth factor B) has been shown to promote endothelial FA uptake by upregulating FA transporters. However, its impact on LPL (lipoprotein lipase)–mediated lipolysis of lipoproteins, a major source of FA for cardiac use, is unknown. Me...

Ketones are alternative energy substrates for the heart and kidney but no studies have investigated their metabolism simultaneously in both organs in humans. The present double tracer positron emission tomography (PET) study evaluated the organ distribution and basal kinetic rates of the radiolabeled ketone, ¹¹C-acetoacetate (¹¹C-AcAc), in the hear...

Background: We previously revealed that oral administration of the β3-adrenergic receptor (AR) agonist mirabegron only elicited small increases in brown adipose tissue (BAT) thermogenesis when ingested at the maximal allowable dose (200 mg). This led to off-target binding of the β1- and β2-AR, thereby increasing cardiovascular responses and white a...

Pharmacological stimulation of human brown adipose tissue (BAT) has been hindered by either ineffective activation or undesirable off-target secondary effects. Oral administration of the maximal allowable dose of mirabegron (200 mg), a β3-adrenergic receptor (β3-AR) agonist, has been effective in stimulating BAT thermogenesis and whole-body energy...

Background Adipocyte hypertrophy is associated with glucose and lipid dysmetabolism, ectopic fat accumulation, and metabolic complications independently of the level of obesity [1]. In this study, we aimed to explore potential mechanisms driving the obesity-independent, hypertrophy-associated dysmetabolism at a single-cell resolution and to assess...

Diets rich in added sugars are associated with metabolic diseases, and studies have shown a link between these pathologies and changes in the microbiome. Given the reported associations in animal models between the microbiome and brown adipose tissue (BAT) function, and the alterations in the microbiome induced by high-glucose or high-fructose diet...

Hepatic de novo lipogenesis is influenced by the branched-chain α-keto acid dehydrogenase (BCKDH) kinase (BCKDK). We aimed to determine whether circulating levels of the immediate substrates of BCKDH, the branched-chain α-ketoacids (BCKAs) and hepatic BCKDK expression are associated with the presence and severity of non-alcoholic fatty liver diseas...

Excessive lean tissue uptake of fatty acids (FA) is important in the development of insulin resistance and may be caused by impaired dietary FA (DFA) storage and/or increased non-esterified FA (NEFA) flux from adipose tissue intracellular lipolysis. Cardiac and hepatic total postprandial FA uptake of NEFA+DFA has, however, never been reported in pr...

Background: The Diabetes Action Canada Training and Mentoring (DAC-TM) Program launched in June 2017, with the goal of building capacity in the next generation of diabetes researchers in Canada in patient-oriented research (POR). Methods: We conducted a program evaluation of the DAC-TM program using a sequential, mixed-methods research design....

Brown adipose tissue (BAT) displays the unique capacity to generate heat through uncoupled oxidative phosphorylation that makes it a very attractive therapeutic target for cardiometabolic diseases. Here, we review BAT cellular metabolism, its regulation by the central nervous and endocrine systems and circulating metabolites, the plausible roles of...

Objective The BETTER registry is a type 1 diabetes population surveillance system co-developed with patient-partners to address the burden of hypoglycemia and assess impact of new therapies and technologies. The aim of the present report was to describe the baseline characteristics of the BETTER registry cohort. Methods Cross-sectional baseline ev...

Aim: Heat therapy is a promising strategy to improve cardiometabolic health. This study evaluated the acute physiological responses to hot water immersion in adults with type 2 diabetes mellitus (T2DM). Methods: On separate days in randomized order, 13 adults with T2DM (8 males/5 females, 62 ± 12 yrs, BMI: 30.1 ± 4.6 kg/m2) were immersed in ther...

Childhood obesity is a growing worldwide problem. In adults, lower cold-induced brown adipose tissue (BAT) activity is linked to obesity and metabolic dysfunction; this relationship remains uncertain in children. In this cross-sectional study, we compared cold-induced supraclavicular (SCV) BAT activity (percent change in proton density fat fraction...

Hepatic de novo lipogenesis is influenced by the branched-chain α-keto acid dehydrogenase (BCKDH) kinase (BCKDK). We aimed to determine whether circulating levels of the immediate substrates of BCKDH, the branched-chain α-ketoacids (BCKAs) and hepatic BCKDK expression are associated with the presence and severity of non-alcoholic fatty liver diseas...

The transcription factor hepatocyte nuclear factor 4 A (HNF4A) controls the metabolic features of several endodermal epithelia. Both HNF4A and HNF4G are redundant in the intestine and it remains unclear whether HNF4A alone controls intestinal lipid metabolism. Here we show that intestinal HNF4A is not required for intestinal lipid metabolism per se...

The advent of deep-learning has set new standards in an array of image translation applications. At present, the use of these methods often requires computer programming experience. Non-commercial programs with graphical interface usually do not allow users to fully customize their deep-learning pipeline. Therefore, our primary objective is to prov...

In rodents, lower brown adipose tissue (BAT) activity is associated with greater liver steatosis and changes in the gut microbiome. However, little is known about these relationships in humans. In adults (n = 60), we assessed hepatic fat and cold-stimulated BAT activity using magnetic resonance imaging and the gut microbiota with 16S sequencing. We...

Obesity contributes to reduced life expectancy because of its link with type 2 diabetes and cardiovascular disease. Yet, targeting this poorly diagnosed, ill-defined, and underaddressed modifiable risk factor remains a challenge. In this review, we emphasize that the tendency among health care professionals to amalgam all forms of obesity altogethe...

Objectives: Arterial hypertension, when exacerbated by excessive dietary salt intake, worsens the morbidity and mortality rates associated with cardiovascular and renal diseases. Stimulation of the apelinergic system appears to protect against several circulatory system diseases, but it remains unknown if such beneficial effects are conserved in se...

The obesity pandemic increasingly causes morbidity and mortality from type 2 diabetes, cardiovascular diseases and many other chronic diseases. Fat cell size (FCS) predicts numerous obesity-related complications such as lipid dysmetabolism, ectopic fat accumulation, insulin resistance, and cardiovascular disorders. Nevertheless, the scarcity of sys...

Objectives The advent of deep-learning has set new standards in an array of image translation applications. At present, the use of these methods often requires computer programming experience. Non-commercial programs with graphical interface usually do not allow users to fully customize their deep-learning pipeline. Therefore, our primary objective...

Sex-related differences in thermoregulatory responses to cold exposure, such as differences in metabolic heat production and fuel selection, are often attributed to differences in morphology and body composition. Whether these differences persist in response to cold when comparing lean, healthy men and women with equivalent total body mass (BM, hea...

The mechanism of increased postprandial nonesterified fatty acid (NEFA) appearance in the circulation in impaired glucose tolerance (IGT) is due to increased adipose tissue lipolysis but could also be contributed to by reduced adipose tissue (AT) dietary fatty acid (DFA) trapping and increased 'spillover' into the circulation. Thirty-one subjects w...

Insulin-like growth factor-binding protein (IGFBP)-2 is a circulating biomarker of cardiometabolic health. Here, we report that circulating IGFBP-2 concentrations robustly increase after different bariatric procedures in humans, reaching higher levels after biliopancreatic diversion with duodenal switch (BPD-DS) than after Roux-en-Y gastric bypass...

There is general agreement that the acute suppression of hepatic glucose production by insulin is mediated by both a direct and an indirect effect on the liver. There is, however, no consensus regarding the relative magnitude of these effects under physiological conditions. Extensive research over the past three decades in humans and animal models...

Insulin inhibits systemic nonesterified fatty acid (NEFA) flux to a greater degree than glucose or any other metabolite. This remarkable effect is mainly due to insulin-mediated inhibition of intracellular triglyceride (TG) lipolysis in adipose tissues and is essential to prevent diabetic ketoacidosis, but also to limit the potential lipotoxic effe...

Enhanced energy expenditure in brown (BAT) and white (WAT) adipose tissues can be therapeutic against metabolic diseases. We examined the thermogenic role of adipose α/β-hydrolase domain-6 (ABHD6), which hydrolyzes monoacylglycerol (MAG), by employing adipose-specific ABHD6-KO mice. Control and KO mice show similar phenotype at room temperature and...

Background Primary care providers’ (PCPs) attitude toward obesity is often negative, and their confidence level for helping patients manage their weight is low. Continuing professional development (CPD) on the subject of obesity is often based on a single activity using a traditional passive approach such as lectures known to have little effect on...

Purpose Determine if dynamic contrast enhanced (DCE) ‐MRI and/or 68 gallium 1,4,7,10‐tetraazacyclododecane N, N′, N″, N‴‐tretraacetic acid (⁶⁸Ga‐DOTA) positron emission tomography (PET) can assess perfusion in rat brown adipose tissue (BAT). Evaluate changes in perfusion between cold‐stimulated and heat‐inhibited BAT. Determine if the ¹¹C‐acetate p...

PurposeBone may regulate glucose homeostasis via uncarboxylated bioactive osteocalcin (ucOCN). This study explored whether changes in ucOCN and bone remodeling are associated with change in glucose homeostasis after biliopancreatic diversion (BPD).Methods In this secondary exploratory analysis of a 1-year prospective observational study, 16 partici...

Stimulation of brown adipose tissue (BAT) thermogenesis in humans has emerged as an attractive target to improve metabolic health. Pharmacological stimulations targeting the β3-adrenergic receptor (β3-AR), the adrenergic receptor believed to mediate BAT thermogenesis, have historically performed poorly in human clinical trials. Here we report that,...

Objective Adaptive thermogenesis, which is partly mediated by sympathetic input on brown adipose tissue (BAT), is a mechanism of heat production that confers protection to prolonged cold exposure. Various endogenous stimuli, including norepinephrine and FGF-21, can also promote the conversion of inguinal white adipocytes to beige adipocytes, which...

Excessive exposure of lean tissues to fatty acids leads to insulin resistance. Proper dietary fatty acids (DFA) storage in white adipose tissue (WAT) is thought to prevent lean tissue lipotoxicity. We showed that WAT storage of DFA was impaired in IGT (impaired glucose tolerance) and was associated with greater cardiac DFA uptake and subclinical le...

Introduction: Excessive exposure of lean tissues to nonesterified fatty acids (NEFA) leads to insulin resistance (IR). Adipocyte hypertrophy is associated with IR and increase in adipose tissue intracellular triglyceride lipolysis and in NEFA levels, that may contribute to hepatic steatosis and IR. The effect of adipocyte hypertrophy on postprandia...

Background HNF4α belongs to the hormone nuclear receptor family and is expressed in liver, intestinal epithelium and pancreas where it regulates genes involved in the control of metabolism. Inactivating mutations in the HNF4A gene cause several forms of maturity-onset diabetes of the young (MODY). However, the specific deletion of Hnf4a in mouse pa...

There is growing interest in the metabolism of ketones owing to their reported benefits in neurological and more recently in cardiovascular and renal diseases. As an alternative to a very high fat ketogenic diet, ketones precursors for oral intake are being developed to achieve ketosis without the need for dietary carbohydrate restriction. Here we...

Reduced storage of dietary fatty acids (DFA) in abdominal adipose tissues with their enhanced cardiac partitioning has been shown in subjects with type 2 diabetes (T2D) and pre-diabetes. We measured DFA metabolism and organ partitioning using positron-emission-tomography with oral and i.v.long-chain fatty acid and glucose tracers during a standard...

Background: Increased myocardial partitioning of dietary fatty acids (DFA) and decreased left-ventricular (LV) function is associated with insulin resistance in prediabetes. Objective: We hypothesized that enhanced myocardial DFA partitioning and reduced LV function may be induced concomitantly with reduced insulin sensitivity upon a 7-day hyper...

Context In rodents, cold exposure induces the activation of brown adipose tissue (BAT) and the induction of intracellular triacylglycerol (TAG) lipolysis. However, in humans, the kinetics of supraclavicular (SCV) BAT activation and the potential importance of TAG stores remain poorly defined. Objective To determine the time course of BAT activatio...

Background: A positive energy balance promotes white adipose tissue (WAT) expansion which is characterized by activation of a repertoire of events including hypoxia, inflammation and extracellular matrix remodelling. The transmembrane glycoprotein CD248 has been implicated in all these processes in different malignant and inflammatory diseases but...

Background [¹¹C]-acetate positron emission tomography is used to assess oxidative metabolism in various tissues including the heart, tumor, and brown adipose tissue. For brown adipose tissue, a monoexponential decay model is commonly employed. However, no systematic assessment of kinetic models has been performed to validate this model or others. T...

Mutations in the HNF4A gene cause MODY1 and are associated with an increased risk of Type 2 diabetes mellitus. On the other hand, incretins are hormones that potentiate reductions in blood glucose levels. Given the established role of incretin-based therapy to treat diabetes and metabolic disorders, we investigated a possible regulatory link betwee...

Background This study evaluated early and medium-term changes in bone turnover markers, and their associations with weight loss, total bone mineral density (BMD), and hormonal changes after biliopancreatic diversion (BPD). Methods Ancillary study from a one-year prospective cohort of 16 individuals assessed before, 3 days, 3 and 12 months after BP...

Autotaxin (ATX), an adipose tissue-derived lysophospholipase, has been involved in the pathophysiology of cardiometabolic diseases. The impact of bariatric surgery on circulating ATX levels is unknown. We examined the short- (24 h, 5 days) and longer-term (6 and 12 months) impact of bariatric surgery; as well as the short-term effect of caloric res...

Unacylated ghrelin (UAG), the most abundant form of ghrelin in circulation, has been shown to exert cardioprotective effect in experimental cardiopathies. The present study aimed to investigate the cardioprotective effect of a linear bioactive fragment of UAG against myocardial ischemia-induced injury and dysfunction in C57BL/6 wild type mice and t...

The demonstration of metabolically active brown adipose tissue (BAT) in humans primarily using positron emission tomography coupled to computed tomography (PET/CT) with the glucose tracer 18-fluorodeoxyglucose (¹⁸FDG) has renewed the interest of the scientific and medical community in the possible role of BAT as a target for the prevention and trea...

The activation of brown adipose tissue (BAT) is associated with reductions in circulating lipids and glucose in rodents and contributes to energy expenditure in humans indicating the potential therapeutic importance of targetting this tissue for the treatment of a variety of metabolic disorders. In order to evaluate the therapeutic potential of hum...

Postprandial dietary fatty acid (FA) biodistribution is impaired in subjects with glucose intolerance, with decreased FA storage in adipose tissues (AT) and increased FA uptake by the myocardium. These abnormalities are improved after 1 year of lifestyle-induced weight loss. Bariatric surgery leads to early metabolic improvements before weight loss...

Objectives: Mechanisms underlying sepsis-associated encephalopathy remain unclear, but reduced cerebral blood flow, alone or in conjunction with altered autoregulation, is reported as a potential contributor. We compared cerebral blood flow of control subjects and vasopressor-dependent septic patients. Design: Randomized crossover study. Settin...

Patients with diabetes are at very high risk of hospitalization and death from heart failure. Increased prevalence of coronary heart disease, hypertension, autonomic neuropathy and kidney failure all play a role in this increased risk. However, cardiac metabolic abnormalities are now recognized to play a role in this increased risk. Increased relia...

The epidemic of type 2 diabetes mellitus (T2DM) is fueled by added fructose consumption. Here, we thus combined high-fat/high-fructose diet, with multiple low-dose injections of streptozotocin (HF/HF/Stz) to emulate the long-term complications of T2DM. HF/HF/Stz rats, monitored over 56 weeks, exhibited metabolic dysfunctions associated with the dif...

Background We investigate the use of different denoising filters on low signal-to-noise ratio cardiac images of the rat heart acquired with a birdcage volume coil at 7T. Accuracy and variability of cardiac function parameters were measured from manual segmentation of rat heart images with and without filtering. Methods Ten rats were studied using a...

Objectives: Enhanced mitochondrial fatty acid utilization is known to increase radical oxidative stress and induce insulin resistance. An increased level of plasma acylcarnitine (AC) has been proposed to indicate mitochondrial energy substrate overload, a possible mechanism leading to insulin resistance. The aim of our study was to determine fasti...

CD36 is a multiligand receptor involved in lipid metabolism. We investigated the mechanisms underlying the cardioprotective effect of CP-3(iv), an azapeptide belonging to a new class of selective CD36 ligands. The role of CP-3(iv) in mediating cardioprotection was investigated because CD36 signaling leads to activation of peroxisome proliferator-ac...

Context Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a key regulator of low-density lipoprotein cholesterol (LDL-C) concentrations. In patients with severe obesity, biliopancreatic diversion with duodenal switch (BPD-DS) surgery induces substantial weight loss and favourably influence lipoprotein metabolism. The impact of BPD-DS surgery...

Hypertrophic remodelling of white adipose tissues is associated with lean organs overexposure to circulating triglycerides (TG) and non-esterified fatty acids (NEFA), ultimately leading to insulin resistance. Bariatric surgery promotes type 2 diabetes (T2D) remission by a succession of weight-loss dependent and independent mechanisms. However, the...

Background Type 2 diabetes is one of the leading non-infectious diseases worldwide and closely relates to excess adipose tissue accumulation as seen in obesity. Specifically, hypertrophic expansion of adipose tissues is related to increased cardiometabolic risk leading to type 2 diabetes. Studying mechanisms underlying adipocyte hypertrophy could l...