Fatty Acid Metabolic Remodeling During Type 2 Diabetes Remission After Bariatric Surgery

Grenier-Larouche, Thomas; Carreau, Anne‐Marie; Géloën, Alain; Frisch, Frédérique; Biertho, Laurent; Marceau, Simon; Lebel, Stéfane; Hould, Frédéric‐Simon; Richard, Denis; Tchernof, André; Carpentier, André C.

doi:10.2337/db17-0414

Cited by 26 publications

(24 citation statements)

References 47 publications

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“…However, adaptation of WAT TG/fatty acid cycling can reach impressive levels in humans. For example, using stable isotope tracer methodology in morbidly obese subjects before and 3 days, 3 months and 1 year after they underwent bariatric surgery, we showed that WAT NEFA production rate and storage capacity can be sustained at the same level despite a more than 3-fold reduction in adipose tissue mass ( 229 ), likely resulting in much enhanced energy expenditure per adipose tissue mass. Whether such WAT adaptations may contribute to chronic shift of total body energy balance remains to be tested.…”

Section: Is There a Contribution Of Wat Browning To Thermogenesis Andmentioning

confidence: 96%

Brown Adipose Tissue Energy Metabolism in Humans

et al. 2018

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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 treatment of obesity and type 2 diabetes (T2D). Here, we offer a comprehensive review of BAT energy metabolism in humans. Considerable advances in methods to measure BAT energy metabolism, including nonesterified fatty acids (NEFA), chylomicron-triglycerides (TG), oxygen, Krebs cycle rate, and intracellular TG have led to very good quantification of energy substrate metabolism per volume of active BAT in vivo. These studies have also shown that intracellular TG are likely the primary energy source of BAT upon activation by cold. Current estimates of BAT's contribution to energy expenditure range at the lower end of what would be potentially clinically relevant if chronically sustained. Yet, 18FDG PET/CT remains the gold-standard defining method to quantify total BAT volume of activity, used to calculate BAT's total energy expenditure. Unfortunately, BAT glucose metabolism better reflects BAT's insulin sensitivity and blood flow. It is now clear that most glucose taken up by BAT does not fuel mitochondrial oxidative metabolism and that BAT glucose uptake can therefore be disconnected from thermogenesis. Furthermore, BAT thermogenesis is efficiently recruited upon repeated cold exposure, doubling to tripling its total oxidative capacity, with reciprocal reduction of muscle thermogenesis. Recent data suggest that total BAT volume may be much larger than the typically observed 50–150 ml with 18FDG PET/CT. Therefore, the current estimates of total BAT thermogenesis, largely relying on total BAT volume using 18FDG PET/CT, may underestimate the true contribution of BAT to total energy expenditure. Quantification of the contribution of BAT to energy expenditure begs for the development of more integrated whole body in vivo methods.

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Section: Is There a Contribution Of Wat Browning To Thermogenesis Andmentioning

confidence: 96%

Brown Adipose Tissue Energy Metabolism in Humans

et al. 2018

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“…Putative mechanisms have been hypothesized to explain the observed links between acylcarnitines, obesity, and diabetes [ 43 ]. Bariatric surgery has been associated with improved type 2 diabetes and major metabolic alterations, including fatty acid metabolism [ 43 , 44 ]. Medium- and long-chain fatty acids are transported as acylcarnitines across mitochondrial membranes for β-oxidation [ 6 , 45 ].…”

Section: Discussionmentioning

confidence: 99%

“…Medium- and long-chain fatty acids are transported as acylcarnitines across mitochondrial membranes for β-oxidation [ 6 , 45 ]. Dodecanoylcarnitine and other acylcarnitines have a key role in fatty acid β-oxidation and have been hypothesized to indicate metabolic flexibility [ 43 , 44 ].…”

Section: Discussionmentioning

confidence: 99%

Metabolomic Profiling After a Meal Shows Greater Changes and Lower Metabolic Flexibility in Cardiometabolic Diseases

Jones

et al. 2020

Journal of the Endocrine Society

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Context Metabolic flexibility is the physiologic acclimatization to differing energy availability and requirement states. Effectively maintaining metabolic flexibility remains challenging, particularly since metabolic dysregulations in meal consumption during CMD pathophysiology are incompletely understood. Objective We compared metabolic flexibility following consumption of a standardized meal challenge among adults with or without CMDs. Design, Setting, and Participants Study participants (n=349; 37-54 years, 55% female) received a standardized meal challenge (520 kcal, 67.4 g carbohydrates, 24.3 g fat, 8.0 g protein; 259 mL). Blood samples were collected at baseline and two hours post-challenge. Plasma samples were assayed by high-resolution, non-targeted metabolomics with dual column liquid chromatography and ultra-high-resolution mass spectrometry. Metabolome-wide associations between features and meal challenge timepoint were assessed in multivariable linear regression models. Results Sixty-five percent of participants had ≥ one of four CMDs; 33% were obese, 6% had diabetes, 39% had hypertension, and 50% had metabolic syndrome. Log2-normalized ratios of feature peak areas (post-prandial:fasting) clustered separately among participants with versus without any CMDs. Among participants with CMDs, the meal challenge altered 1,756 feature peak areas (1,063 C18, 693 HILIC; all q<0.05). In individuals without CMDs, the meal challenge changed 1,383 feature peak areas (875 C18, 508 HILIC; all q<0.05). There were 108 features (60 C18, 48 HILIC) that differed by the meal challenge and CMD status, including dipeptides, carnitines, glycerophospholipids, and a bile acid metabolite (all p<0.05). Conclusions Among adults with CMDs, more metabolomic features differed after a meal challenge which reflected lower metabolic flexibility, relative to individuals without CMDs.

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“…Uncarboxylated osteocalcin ELISA. A sandwich enzyme-linked immunosorbent assay (ELISA) recognizing human ucOCN was established in collaboration with BioLegend Inc. using the 8H4 (anti-C-terminal) as a capture antibody and biotinylated 4B6 (anti-ucOCN [12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28] as the detection antibody (Cat. No.…”

Section: Methodsmentioning

confidence: 99%

Measurement of bioactive osteocalcin in humans using a novel immunoassay reveals association with glucose metabolism and β-cell function

Lacombe

Rifai

Loter

et al. 2020

American Journal of Physiology-Endocrinology and Metabolism

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Osteocalcin (OCN) is a bone-derived hormone involved in the regulation of glucose metabolism. In serum, OCN exists in carboxylated and uncarboxylated forms (ucOCN), and studies in rodents suggest that ucOCN is the bioactive form of this hormone. Whether this is also the case in humans is unclear, because a reliable assay to measure ucOCN is not available. Here, we established and validated a new immunoassay (ELISA) measuring human ucOCN and used it to determine the level of bioactive OCN in two cohorts of overweight or obese subjects, with or without type 2 diabetes (T2D). The ELISA could specifically detect ucOCN concentrations ranging from 0.037 to 1.8 ng/mL. In a first cohort of overweight or obese postmenopausal women without diabetes ( n = 132), ucOCN correlated negatively with fasting glucose (r = −0.18, P = 0.042) and insulin resistance assessed by the homeostatic model assessment of insulin resistance (r = −0.18, P = 0.038) and positively with insulin sensitivity assessed by a hyperinsulinemic-euglycemic clamp (r = 0.18, P = 0.043) or insulin sensitivity index derived from an oral glucose tolerance test (r = 0.26, P = 0.003). In a second cohort of subjects with severe obesity ( n = 16), ucOCN was found to be lower in subjects with T2D compared with those without T2D (2.76 ± 0.38 versus 4.52 ± 0.06 ng/mL, P = 0.009) and to negatively correlate with fasting glucose (r = −0.50, P = 0.046) and glycated hemoglobin (r = −0.57, P = 0.021). Moreover, the subjects with ucOCN levels below 3 ng/mL had a reduced insulin secretion rate during a hyperglycemic clamp ( P = 0.03). In conclusion, ucOCN measured with this novel and specific assay is inversely associated with insulin resistance and β-cell dysfunction in humans.

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Fatty Acid Metabolic Remodeling During Type 2 Diabetes Remission After Bariatric Surgery

Cited by 26 publications

References 47 publications

Brown Adipose Tissue Energy Metabolism in Humans

Brown Adipose Tissue Energy Metabolism in Humans

Metabolomic Profiling After a Meal Shows Greater Changes and Lower Metabolic Flexibility in Cardiometabolic Diseases

Measurement of bioactive osteocalcin in humans using a novel immunoassay reveals association with glucose metabolism and β-cell function

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