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Nutrients
Volume 18
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10.3390/nu18010057
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Article

Dihomo-γ-Linolenic Acid Elevation with Desaturase Imbalance in Metabolic Dysfunction-Associated Steatotic Liver Disease in a Japanese Health Checkups Cohort: HOZUGAWA Study, a Multi-Omic, Diet Adjusted Analysis

by
Sayaka Kawai
1,
Hiroshi Okada
1,
Hideto Okamoto
1,
Ren Yashiki
1,
Megumi Minamida
1,
Natsuko Shinagawa
1,
Takahiro Ichikawa
1,
Shinta Yamamoto
1,
Noriyuki Kitagawa
2,
Yoshitaka Hashimoto
3,
Ryoichi Sasano
4,
Kunimasa Yagi
5,
Masahide Hamaguchi
1,* and
Michiaki Fukui
1
1
Department of Endocrinology and Metabolism, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan
2
Department of Diabetology, Kameoka Municipal Hospital, Kyoto 621-8585, Japan
3
Department of Diabetes and Endocrinology, Matsushita Memorial Hospital, Moriguchi 570-8540, Japan
4
AiSTI SCIENCE Co., Ltd., Wakayama 640-8390, Japan
5
Department of Internal Medicine, Kanazawa Medical University Hospital, 1-1 Daigaku, Uchinada-machi 920-0293, Japan
*
Author to whom correspondence should be addressed.
Nutrients 2026, 18(1), 57; https://doi.org/10.3390/nu18010057
Submission received: 1 December 2025 / Revised: 20 December 2025 / Accepted: 21 December 2025 / Published: 23 December 2025
(This article belongs to the Special Issue Lipid Metabolism and Nutritional Status in Patients Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD))
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Abstract

Background/Objectives: Metabolic dysfunction-associated steatotic liver disease (MASLD) has been linked to dietary fat quality and polyunsaturated fatty-acid metabolism. We evaluated whether dietary n-6 fatty-acid intake, serum dihomo-γ-linolenic acid (DGLA), and desaturase-based indices for Δ5-desaturase (D5D) and Δ6-desaturase (D6D) are associated with MASLD. Methods: We conducted a cross-sectional analysis within the HOZUGAWA health checkup cohort in Japan (n = 289; 100 MASLD, 189 non-MASLD). Participants underwent hepatic ultrasonography, dietary assessment using the Brief Self-Administered Diet History Questionnaire, and fasting serum metabolomics by gas chromatography–mass spectrometry with solid-phase dehydration derivatization. Enzyme indices were defined as the D5D index = arachidonic acid/DGLA and the D6D proxy index = DGLA/linoleic acid (hereafter referred to as the D6D index) because γ-linolenic acid was not measured. Natural-log-transformed D5D index, D6D index, DGLA, and total dietary n-6 fatty-acid intake were entered into multivariable logistic regression models for MASLD adjusted for age, sex, BMI, alcohol intake, and total energy. Results: Compared with non-MASLD, MASLD showed higher serum DGLA, lower D5D index, and higher D6D index (all p ≤ 0.005), with no between-group differences in total energy intake, linoleic acid, total polyunsaturated fatty acids, or total dietary n-6 fatty-acid intake. Higher ln D5D was independently associated with lower odds of MASLD (OR 0.62, 95% CI 0.42–0.86), whereas higher ln D6D index (OR 1.42, 95% CI 1.04–1.95) and ln DGLA (OR 1.62, 95% CI 1.13–2.43) were each positively associated. Total dietary n-6 fatty-acid intake was not independently associated with MASLD. Conclusions: In this Japanese health examination cohort, an imbalance in estimated desaturase activities—lower D5D index and higher D6D index—together with higher serum DGLA was independently associated with MASLD, whereas n-6 intake showed no group difference or independent association. These findings suggest that enzyme-linked endogenous n-6 metabolic status may be more closely related to the MASLD phenotype than intake quantity alone.
Keywords: MASLD; dihomo-γ-linolenic acid (DGLA); Δ5-desaturase (D5D); Δ6-desaturase (D6D); linoleic acid; n-6 polyunsaturated fatty acids; metabolomics; GC–MS; Japanese cohort MASLD; dihomo-γ-linolenic acid (DGLA); Δ5-desaturase (D5D); Δ6-desaturase (D6D); linoleic acid; n-6 polyunsaturated fatty acids; metabolomics; GC–MS; Japanese cohort

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MDPI and ACS Style

Kawai, S.; Okada, H.; Okamoto, H.; Yashiki, R.; Minamida, M.; Shinagawa, N.; Ichikawa, T.; Yamamoto, S.; Kitagawa, N.; Hashimoto, Y.; et al. Dihomo-γ-Linolenic Acid Elevation with Desaturase Imbalance in Metabolic Dysfunction-Associated Steatotic Liver Disease in a Japanese Health Checkups Cohort: HOZUGAWA Study, a Multi-Omic, Diet Adjusted Analysis. Nutrients 2026, 18, 57. https://doi.org/10.3390/nu18010057

AMA Style

Kawai S, Okada H, Okamoto H, Yashiki R, Minamida M, Shinagawa N, Ichikawa T, Yamamoto S, Kitagawa N, Hashimoto Y, et al. Dihomo-γ-Linolenic Acid Elevation with Desaturase Imbalance in Metabolic Dysfunction-Associated Steatotic Liver Disease in a Japanese Health Checkups Cohort: HOZUGAWA Study, a Multi-Omic, Diet Adjusted Analysis. Nutrients. 2026; 18(1):57. https://doi.org/10.3390/nu18010057

Chicago/Turabian Style

Kawai, Sayaka, Hiroshi Okada, Hideto Okamoto, Ren Yashiki, Megumi Minamida, Natsuko Shinagawa, Takahiro Ichikawa, Shinta Yamamoto, Noriyuki Kitagawa, Yoshitaka Hashimoto, and et al. 2026. "Dihomo-γ-Linolenic Acid Elevation with Desaturase Imbalance in Metabolic Dysfunction-Associated Steatotic Liver Disease in a Japanese Health Checkups Cohort: HOZUGAWA Study, a Multi-Omic, Diet Adjusted Analysis" Nutrients 18, no. 1: 57. https://doi.org/10.3390/nu18010057

APA Style

Kawai, S., Okada, H., Okamoto, H., Yashiki, R., Minamida, M., Shinagawa, N., Ichikawa, T., Yamamoto, S., Kitagawa, N., Hashimoto, Y., Sasano, R., Yagi, K., Hamaguchi, M., & Fukui, M. (2026). Dihomo-γ-Linolenic Acid Elevation with Desaturase Imbalance in Metabolic Dysfunction-Associated Steatotic Liver Disease in a Japanese Health Checkups Cohort: HOZUGAWA Study, a Multi-Omic, Diet Adjusted Analysis. Nutrients, 18(1), 57. https://doi.org/10.3390/nu18010057

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