Adiponectin/leptin ratio increases after a 12-week very low-carbohydrate, high-fat diet, and exercise training in healthy individuals: A non-randomized, parallel design study

Abstract

This study aimed to investigate the effect of a 12-week very low-carbohydrate, high-fat (VLCHF) diet and exercise on biomarkers of inflammation in healthy individuals. Since the anti-inflammatory effects of a ketogenic diet have been established, we hypothesized that the VLCHF diet, along with exercise, would have an additional favorable effect on biomarkers of inflammation. Twenty-four healthy individuals were allocated to the VLCHF diet (VLCHF: N = 12, age 25.3 ± 2.0 years, body mass 66.7 ± 9.8 kg, fat mass 21.5% ± 4.9%), or habitual diet (HD: N = 12, age 23.9 ± 3.8 years, body mass 72.7 ± 15.0 kg, fat mass 23.4 ± 8.4 %) group. Biomarkers of inflammation (adiponectin, leptin, and high-sensitive interleukin-6 [hs-IL-6]) and substrate metabolism (glycated hemoglobin, fasting glucose, triacylglycerides, and cholesterol) were analyzed from blood at baseline and after 12 weeks. The adiponectin-leptin ratio significantly increased in the VLCHF group after the intervention period (ES [95% CL]: −0.90 [−0.96, −0.77], P ≤ .001, BF₁₀ = 22.15). The adiponectin-leptin ratio changes were associated with both a significant increase in adiponectin (−0.79 [−0.91, −0.54], P ≤ .001, BF₁₀ = 9.43) and a significant decrease in leptin (0.58 [0.19, 0.81], P = .014, BF₁₀ = 2.70). There was moderate evidence of changes in total cholesterol (−1.15 [−2.01, −0.27], P = .010, BF₁₀ = 5.20), and LDL cholesterol (−1.12 [−2.01, −0.21], P = .016, BF₁₀ = 4.56) in the VLCHF group. Body weight (kg) and fat mass (%) decreased in the VLCHF group by 5.4% and 14.9%, respectively. We found that in healthy young individuals, consuming a VLCHF diet while performing regular exercise over a 12-week period produced favorable changes in body weight and fat mass along with beneficial changes in serum adiponectin and leptin concentrations. These data support the use of a VLCHF diet strategy for the primary prevention of chronic diseases associated with systemic low-grade inflammation.

Introduction

Adipose tissue was originally considered a passive organ responsible for insulation, mechanical protection of organs, and storage of excess energy. Today, it is recognized as an active endocrine organ that produces a vast number of biologically active substances termed adipokines, including adiponectin, leptin, and interleukin-6 (IL-6). Adipokines exert local effects on metabolism, regulate whole-body energy homeostasis, and are involved in several metabolic pathways. These adipokines also regulate satiety and appetite, insulin secretion and sensitivity, arterial pressure, and endothelial function [1]. Their dysregulation can cause chronic low-grade inflammatory changes associated with metabolic syndrome, obesity [2,3], cancer [4,5], neurodegenerative diseases [6], and arthritis [3].

Recently, the adiponectin-leptin (Adpn/Lep) ratio has been proposed as a promising marker of adipose tissue dysfunction [7]. An increase in adiposity leads to an increase in leptin levels, but a decrease in adiponectin levels. While leptin generally induces inflammatory responses, adiponectin is considered an anti-inflammatory marker. The imbalance in leptin and adiponectin production caused by increased or dysregulated adiposity may consequently lead to chronic systemic inflammation [8].

Acute inflammatory responses are essential for processes such as wound healing, tissue regeneration, and viral immunity [9]. However, chronic low-grade inflammation at a cellular level can lead to systemic chronic inflammation with an unclear trigger mechanism. Additionally, there is a close relationship between the extent of inflammation and oxidative stress, with an increase in inflammation likely to drive a further increase in oxidative stress and vice versa, thus forming a vicious cycle [10,11]. A high-stress lifestyle alongside aging substantially contributes to the chronic low-grade inflammation profile [12,13]. In addition to these risk factors, the number, intensity, and duration of hyperglycemic events are also considered to accelerate the development of autoimmune diseases, diabetes, and obesity. A high intake of refined carbohydrates (CHO) induces repeated hyperglycemic events, impairing endothelial barrier function. Endothelial dysfunction consequently initiates and maintains several inflammatory mechanisms [14]. Therefore, a very low-carbohydrate, high-fat diet (VLCHF) may represent a promising strategy to prevent or reverse various pathological conditions involving inflammatory and immunological components.

A VLCHF diet is a nutritional approach consisting of restricted CHO consumption and increased fat intake, while protein consumption and total energy intake are preserved [15]. As far as we know, the Adpn/Lep ratio has not been studied in relationship to a VLCHF diet in healthy, nonobese individuals. While adipose tissue dysfunction, characterized by proinflammatory conditions, is not expected in such individuals, a VLCHF diet-induced increase in the Adpn/Lep ratio might still be a beneficial preventive health factor [7]. Therefore, the main aim of this study was to investigate the effects of a 12-week VLCHF diet combined with exercise training on biomarkers of inflammation (adiponectin, leptin, and IL-6) in healthy young individuals. Since the anti-inflammatory effects of a ketogenic diet or caloric restriction have already been established [16,17], we hypothesized that the VLCHF diet would have an additional favorable effect when combined with exercise on the biomarkers of inflammation. This work extends our earlier findings, which focused primarily on exercise performance outcomes [18].