High plasma apolipoprotein B identifies obese subjects who best ameliorate white adipose tissue dysfunction and glucose-induced hyperinsulinemia after a hypocaloric diet

Abstract

Background To optimize the prevention of type 2 diabetes (T2D), high-risk obese subjects with the best metabolic recovery after a hypocaloric diet should be targeted. Apolipoprotein B lipoproteins (apoB lipoproteins) induce white adipose tissue (WAT) dysfunction, which in turn promotes postprandial hypertriglyceridemia, insulin resistance (IR), and hyperinsulinemia. Objective The aim of this study was to explore whether high plasma apoB, or number of plasma apoB lipoproteins, identifies subjects who best ameliorate WAT dysfunction and related risk factors after a hypocaloric diet. Design Fifty-nine men and postmenopausal women [mean ± SD age: 58 ± 6 y; body mass index (kg/m2): 32.6 ± 4.6] completed a prospective study with a 6-mo hypocaloric diet (−500 kcal/d). Glucose-induced insulin secretion (GIIS) and insulin sensitivity (IS) were measured by 1-h intravenous glucose-tolerance test (IVGTT) followed by a 3-h hyperinsulinemic-euglycemic clamp, respectively. Ex vivo gynoid WAT function (i.e., hydrolysis and storage of 3H-triolein–labeled triglyceride-rich lipoproteins) and 6-h postprandial plasma clearance of a 13C-triolein–labeled high-fat meal were measured in a subsample (n = 25). Results Postintervention first-phase GIISIVGTT and total C-peptide secretion decreased in both sexes, whereas second-phase and total GIISIVGTT and clamp IS were ameliorated in men (P < 0.05). Baseline plasma apoB was associated with a postintervention increase in WAT function (r = 0.61) and IS (glucose infusion rate divided by steady state insulin (M/Iclamp) r = 0.30) and a decrease in first-phase, second-phase, and total GIISIVGTT (r = −0.30 to −0.35) without sex differences. The association with postintervention amelioration in WAT function and GIISIVGTT was independent of plasma cholesterol (total, LDL, and HDL), sex, and changes in body composition. Subjects with high baseline plasma apoB (1.2 ± 0.2 g/L) showed a significant increase in WAT function (+105%; P = 0.012) and a decrease in total GIISIVGTT (−34%; P ≤ 0.001), whereas sex-matched subjects with low plasma apoB (0.7 ± 0.1 g/L) did not, despite equivalent changes in body composition and energy intake and expenditure. Conclusions High plasma apoB identifies obese subjects who best ameliorate WAT dysfunction and glucose-induced hyperinsulinemia, independent of changes in adiposity after consumption of a hypocaloric diet. We propose that subjects with high plasma apoB represent an optimal target group for the primary prevention of T2D by hypocaloric diets. This trial was registered at BioMed Central as ISRCTN14476404.

White Adipose Tissue Surface Expression of LDLR and CD36 is Associated with Risk Factors for Type 2 Diabetes in Adults with Obesity

“…The major exclusion criteria were having a Framingham Risk Score ≥ 20%, having chronic disease (including cardiovascular disease, diabetes, and inflammatory disease), and taking medications affecting metabolism. Eighty-two participants completed the principal study (measuring systemic insulin metabolism and inflammation), among whom 32 participants also completed a substudy (measuring WAT function and postprandial fat metabolism) (16). Participants signed consent forms for both studies, which included the conservation and use of their biological samples for 10 years after the study end.…”

“…Insulin sensitivity was assessed as glucose infusion rate divided by steady-state plasma insulin (M/I clamp ) during the hyperinsulinemic-euglycemic clamp. Fasting homeostatic model assessment of insulin resistance (HOMA-IR) was calculated as published (7,12,15,16).…”

The Association of Polyunsaturated Fatty Acid δ-5-Desaturase Activity with Risk Factors for Type 2 Diabetes Is Dependent on Plasma ApoB-Lipoproteins in Overweight and Obese Adults

“…Moreover, acute exposure to native LDLs reduces the hydrolysis and storage of TG-rich lipoproteins (TRLs) in murine adipocytes and human white adipose tissue (WAT) ex vivo (3,7). In line, plasma apoB is associated with reduced WAT function (3,(7)(8)(9) and related risk factors for T2D, namely IR (7)(8)(9)(10), elevated glucose-induced insulin secretion (GIIS) (7)(8)(9)(10), postprandial hypertriglyceridemia (3,(7)(8)(9), and systemic inflammation (10,11) independent of body composition in overweight and obese subjects. Epidemiologic evidence confirms that plasma apoB predicts the incidence of T2D 3-10 y before its onset in several populations independent of traditional risk factors including obesity, waist circumference, and plasma glycemia (12)(13)(14)(15).…”

“…Before the Botnia clamp, subjects were instructed to follow a 3-d high-carbohydrate diet to maximize glycogen stores and ensure that glucose infusion during the clamp is used for oxidation rather than storage as published (7)(8)(9)(10)35). Subjects were given written instruction on the carbohydrate exchanges needed to achieve 300 g/d for men and 225 g/d for women, and were reminded by phone to follow the highcarbohydrate diet 3-d before the clamp.…”

Mitochondrial aconitase controls adipogenesis through mediation of cellular ATP production

“…Mitochondrial function is essential for normal WAT 5‐8 . WAT shows low energy consumption, 9,10 but mitochondria are necessary for maintaining white adipocyte metabolic homeostasis 7 . The TCA cycle is a key metabolic pathway that degrades carbohydrate, fat, and protein metabolites and generates NADH and FADH2.…”